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Morawska-Kozłowska M, Pitas M, Zhalniarovich Y. Mesenchymal Stem Cells in Veterinary Medicine-Still Untapped Potential. Animals (Basel) 2025; 15:1175. [PMID: 40282009 PMCID: PMC12024326 DOI: 10.3390/ani15081175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 04/05/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025] Open
Abstract
Mesenchymal stem cells (MSCs) hold significant therapeutic potential in veterinary medicine due to their regenerative and immunomodulatory properties. This review examines the clinical applications of MSCs across multiple animal species, including equine, canine, feline, and bovine medicine. MSC therapies have demonstrated promising outcomes in treating musculoskeletal disorders, osteoarthritis, inflammatory diseases, and tissue injuries, particularly in horses and dogs. In cats, MSCs show potential for managing chronic kidney disease, inflammatory bowel disease, and asthma, while in bovine medicine, they offer alternative treatment approaches for mastitis and orthopedic injuries. Despite these advancements, challenges such as treatment standardization, cell sourcing, and potential adverse effects, including tumorigenicity, remain under investigation. The emerging field of MSC-based veterinary medicine highlights its capacity to enhance healing, reduce inflammation, and improve clinical outcomes. However, further research is necessary to optimize treatment protocols and address safety concerns, ensuring the widespread adoption of MSC therapies in veterinary practice.
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Affiliation(s)
- Magdalena Morawska-Kozłowska
- Department of Surgery and Radiology with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland;
| | - Mateusz Pitas
- Veterinary Polyclinic, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland;
| | - Yauheni Zhalniarovich
- Department of Surgery and Radiology with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland;
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Klymiuk MC, Speer J, Marco ID, Elashry MI, Heimann M, Wenisch S, Arnhold S. Determination of the miRNA profile of extracellular vesicles from equine mesenchymal stem cells after different treatments. Stem Cell Res Ther 2025; 16:162. [PMID: 40188160 PMCID: PMC11972531 DOI: 10.1186/s13287-025-04287-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 03/19/2025] [Indexed: 04/07/2025] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a common and incurable disease in humans and animals. To gain a better understanding of the pathogenesis and identify potential treatments, miRNAs will be extracted and analysed from extracellular vesicles (EVs) of equine adipose derived mesenchymal stem cells (AdMSCs). METHODS For this purpose we cultivated and pretreated AdMSCs under different conditions: interleukin 1β, shock wave, chondrogenic differentiation, chondrogenic differentiation under hypoxia, or after senescence. After treatment, EVs were harvested from the cell culture supernatants. Next-generation sequencing (NGS) was used to sequence the miRNAs from the EVs. RESULTS A total of 89 miRNAs whose expression was significantly altered compared with that of an untreated negative control were identified. On average, 53 miRNAs were upregulated and 6 miRNAs were downregulated. Among others, the miRNAs eca-miR-101, eca-miR-143, eca-miR-145, eca-miR-146a, eca-miR-27a, eca-miR-29b, eca-miR-93, eca-miR-98, and eca-miR-221 were significantly increased after the stimulations, which, as known anti-inflammatory miRNAs, could be candidates for therapeutic use in the treatment of OA. CONCLUSION These results lay the foundation for further research into the significance and efficacy of these miRNAs so that this knowledge can be improved in further experiments and, ideally, translated into therapeutic use.
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Affiliation(s)
- Michele C Klymiuk
- Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany.
| | - Julia Speer
- Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany
| | - Isabelle De Marco
- Clinic of Small Animals, c/o Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany
| | - Mohamed I Elashry
- Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany
| | - Manuela Heimann
- Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany
| | - Sabine Wenisch
- Clinic of Small Animals, c/o Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany
| | - Stefan Arnhold
- Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Strasse 98, 35392, Giessen, Germany
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Guerra-Gomes M, Ferreira-Baptista C, Barros J, Alves-Pimenta S, Gomes P, Colaço B. Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals. Animals (Basel) 2025; 15:589. [PMID: 40003071 PMCID: PMC11851989 DOI: 10.3390/ani15040589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/07/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Stifle joint diseases present a significant challenge in companion animals that often lead to hind limb lameness, with osteoarthritis being a prevalent degenerative condition causing pain and reduced mobility. Regenerative medicine offers a promising avenue for improving treatment outcomes, with a range of emerging therapies showing potential to alleviate symptoms and promote joint health. Among these, hyaluronic acid and platelet-rich plasma have been widely used as intra-articular treatments to enhance joint lubrication, reduce inflammation, and provide symptomatic relief. Interleukin-1 receptor antagonist protein, autologous conditioned serum, and autologous protein solution represent the next generation of regenerative therapies, offering more disease-modifying effects by inhibiting key mediators of joint inflammation. More recently, the MSC-derived secretome has emerged as an innovative, cell-free approach that leverages the diverse bioactive factors secreted by MSCs to support tissue repair and modulate inflammation. This review highlights the evidence base behind these non-cellular orthobiologic treatments for stifle joint disease, aiming to inform veterinary practitioners and owners about available options and their efficacy in supporting conventional treatments.
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Affiliation(s)
- Maria Guerra-Gomes
- i3S—Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (M.G.-G.); (J.B.)
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Carla Ferreira-Baptista
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Joana Barros
- i3S—Institute for Research and Innovation in Health, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (M.G.-G.); (J.B.)
| | - Sofia Alves-Pimenta
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Pedro Gomes
- BoneLab, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal; (C.F.-B.); (P.G.)
- LAQV/REQUIMTE, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
| | - Bruno Colaço
- CECAV—Veterinary and Animal Research Centre UTAD, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
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Li G, He F, Feng J, Xu G, Wu C, Qiao Y, Liu Y, Chen H, Du P, Wang J. Injectable Self-Assembling Procyanidin Nanospheres for Effective Osteoarthritis Treatment. Int J Nanomedicine 2025; 20:1133-1145. [PMID: 39895981 PMCID: PMC11787779 DOI: 10.2147/ijn.s496827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 01/22/2025] [Indexed: 02/04/2025] Open
Abstract
Background Osteoarthritis (OA), a prevalent joint disease, causes immense suffering to thousands of patients, impairing their mobility and diminishing their quality of life. Current treatment methods primarily rely on analgesics or anti-inflammatory drugs to alleviate symptoms but fail to achieve the desired therapeutic outcome. Methods To better realize therapeutic effects of OA, procyanidins (PAs), as a type of plant flavonoids with strong antioxidant and anti-inflammatory activities, were designed to self-assembly with well-dispersible Pluronic F127 (PF127) through the hydrogen-bond interaction to present an injectable, biocompatibility PA nanospheres. Results These nanospheres significantly increased the cell viability in mouse L929 fibroblasts and ADTC5 chondrocytes compared with unassembled PAs. In addition, the self-assembling PAs/PF127 nanospheres enhanced the protein expression of collagen (COL1A1 and COL3A1) in fibroblasts, and the expression of glycosaminoglycan and COL2A1 was also higher than unassembled PAs in chondrocytes, this heralded the potential to achieve OA repair strategies at the cellular level. In an enzymolysis model of rat OA, PAs/PF127 nanospheres significantly reduce joint space swelling in the early stages of cartilage destruction and accelerate the formation of subchondral bone and cartilaginous surface. Implication This study offers valuable insights into the preparation of novel PA nanospheres for effective repair of OA.
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Affiliation(s)
- Guangjie Li
- The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
- College of Civil Engineering and Mechanics, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Fei He
- College of Civil Engineering and Mechanics, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Jianbao Feng
- Hospital of Stomatology, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Ge Xu
- The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Chengye Wu
- The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Yufei Qiao
- The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Yang Liu
- Hospital of Stomatology, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Hanlin Chen
- The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
| | - Pengcheng Du
- College of Chemistry and Chemical Engineering, Lanzhou University, Gansu Province, People’s Republic of China
| | - Jizeng Wang
- College of Civil Engineering and Mechanics, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China
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Sabucedo-Suárez A, López-Peña M, Permuy M, Muñóz F. Soybean and avocado unsaponifiables: a review of their potential use in the treatment of osteoarthritis. Front Vet Sci 2025; 11:1473688. [PMID: 39881723 PMCID: PMC11776088 DOI: 10.3389/fvets.2024.1473688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 11/26/2024] [Indexed: 01/31/2025] Open
Abstract
Recent research has shown that Avocado-Soybean Unsaponifiables (ASU) greatly reduce the symptoms of osteoarthritis (OA). It's yet unknown exactly how ASU works, however, it has been demonstrated to have analgesic and anti-inflammatory effects. These qualities can potentially lessen the need for non-steroidal anti-inflammatory medicines (NSAIDs) and their secondary effects. This review aims to examine the current literature on ASU, focusing on their efficacy, mechanism of action, and potential utility in treating OA for managing chronic pain associated with this condition. The literature review was conducted manually through Pubmed, Scopus and Web of Science (WOS) databases, covering studies from 2000 to 2022 with terms like "osteoarthritis," "OA," "animal models," "ASU," and "soy/avocado." Two reviewers independently screened each article using inclusion and exclusion criteria and categorized the studies into in vitro, preclinical, and clinical groups. According to in vitro research, ASU affect the regulation of molecules related to OA, increasing structural elements like collagen and aggrecan and decreasing pro-inflammatory mediators. Although results vary, pre-clinical research in different animal models has demonstrated positive effects, such as ameliorating histopathological changes and reduced inflammation. Despite some discrepancies regarding structural changes in the joints, clinical trials typically demonstrate symptom relief and slow down the disease progression. While ASU demonstrates significant promise in alleviating OA symptoms and reducing reliance on NSAIDs, further research is essential to fully understand its mechanisms of action. More studies are needed to determine the precise pathways through which ASU exerts its effects and to establish the most effective dosages for its administration, either alone or in combination with other treatments.
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Affiliation(s)
- Ana Sabucedo-Suárez
- Departamento de Anatomía, Producción Animal e Ciencias Clínicas Veterinarias, Facultade de Veterinaria, Campus Terra, Universidade de Santiago de Compostela, Lugo, Spain
- IboneLab S.L., Laboratory of Biomaterials, Lugo, Spain
| | - Mónica López-Peña
- Departamento de Anatomía, Producción Animal e Ciencias Clínicas Veterinarias, Facultade de Veterinaria, Campus Terra, Universidade de Santiago de Compostela, Lugo, Spain
- IboneLab S.L., Laboratory of Biomaterials, Lugo, Spain
| | - María Permuy
- Departamento de Anatomía, Producción Animal e Ciencias Clínicas Veterinarias, Facultade de Veterinaria, Campus Terra, Universidade de Santiago de Compostela, Lugo, Spain
- IboneLab S.L., Laboratory of Biomaterials, Lugo, Spain
| | - Fernando Muñóz
- Departamento de Anatomía, Producción Animal e Ciencias Clínicas Veterinarias, Facultade de Veterinaria, Campus Terra, Universidade de Santiago de Compostela, Lugo, Spain
- IboneLab S.L., Laboratory of Biomaterials, Lugo, Spain
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Ghamrawi A, Basso R, Shakik N, Haddad L, Nasr Z, Harmouch C. Wharton's Jelly Mesenchymal Stem Cells: Shaping the Future of Osteoarthritis Therapy with Advancements in Chitosan-Hyaluronic Acid Scaffolds. Stem Cells Dev 2025; 34:1-16. [PMID: 39605205 DOI: 10.1089/scd.2024.0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024] Open
Abstract
This review explores the potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in cartilage regeneration and osteoarthritis treatment. It covers key factors influencing chondrogenesis, including growth factors, cytokines, and hypoxia, focusing on precise timing. The effectiveness of three-dimensional cultures and scaffold-based strategies in chondrogenic differentiation is discussed. Specific biomaterials such as chitosan and hyaluronic acid are highlighted for tissue engineering. The document reviews clinical applications, incorporating evidence from animal research and early trials and molecular and histological assessments of chondrogenic differentiation processes. It addresses challenges and strategies for optimizing MSC-derived chondrocyte therapy, emphasizing the immunomodulatory properties of these cells. The review concludes as a comprehensive road map for future research and clinical applications in regenerative medicine.
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Affiliation(s)
- Ahed Ghamrawi
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Rasha Basso
- Department of Medical Laboratory Sciences, Faculty of Health Sciences University of Balamand, Beirut, Lebanon
| | - Nour Shakik
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Lara Haddad
- Department of Medical Laboratory Sciences, Faculty of Health Sciences University of Balamand, Beirut, Lebanon
| | - Zeina Nasr
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
| | - Chaza Harmouch
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon
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7
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Bai H, Liu T, Wang H, Li Y, Wang Z. Chondroitin sulfate alleviated lipopolysaccharide-induced arthritis in feline and canine articular chondrocytes through regulation of neurotrophic signaling pathways and apoptosis. Tissue Cell 2024; 91:102642. [PMID: 39603024 DOI: 10.1016/j.tice.2024.102642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 11/06/2024] [Accepted: 11/25/2024] [Indexed: 11/29/2024]
Abstract
Osteoarthritis (OA) is a pervasive degenerative joint disease affecting companion animals, characterized by chronic inflammation and cartilage degradation. However, the effectiveness of chondroitin sulfate (CS) in treating OA in dogs and cats remains controversial. This study aimed to determine the therapeutic effects and molecular mechanisms of CS on lipopolysaccharide (LPS)-induced inflammation in feline and canine articular chondrocytes (FAC and CAC) at the cellular level in vitro. Our findings demonstrated that CS treatment (800 µg/mL) significantly enhanced cell viability and reduced oxidative stress in FAC and CAC, as evidenced by decreased levels of reactive oxygen species and increased activities of antioxidant enzymes. Furthermore, CS treatment effectively suppressed LPS-induced secretion of pro-inflammatory cytokines, including interleukin-1, tumor necrosis factor-α, interleukin-8, interleukin-10, and matrix metalloproteinases-3, and reduced apoptosis, as confirmed by fluorescence staining and flow cytometry. Transcriptomic analysis revealed that CS upregulated neurotrophic signaling pathways, promoting cell survival and proliferation. Metabolomic analysis indicated that CS treatment upregulated metabolites associated with glycerophospholipid and purine metabolism, suggesting enhanced membrane integrity and energy metabolism. Conversely, pathways involved in protein catabolism and arachidonic acid metabolism were downregulated, indicating a reduction in inflammatory mediators. Collectively, these findings elucidate the multifaceted role of CS in modulating chondrocyte metabolism and inflammatory responses, highlighting its potential to alleviate OA.
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Affiliation(s)
- Huasong Bai
- Nourse Science Centre for Pet Nutrition, Wuhu 241200, PR China
| | - Tong Liu
- Nourse Science Centre for Pet Nutrition, Wuhu 241200, PR China
| | - Hengyan Wang
- Nourse Science Centre for Pet Nutrition, Wuhu 241200, PR China
| | - Yunliang Li
- School of Food and Biological Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, PR China.
| | - Zhanzhong Wang
- Nourse Science Centre for Pet Nutrition, Wuhu 241200, PR China.
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Stabile M, Fracassi L, Lacitignola L, Garcia-Pedraza E, Girelli CR, Calculli C, D’Uggento AM, Ribecco N, Crovace A, Fanizzi FP, Staffieri F. Effects of a feed supplement, containing undenatured type II collagen (UC II®) and Boswellia Serrata, in the management of mild/moderate mobility disorders in dogs: A randomized, double-blind, placebo controlled, cross-over study. PLoS One 2024; 19:e0305697. [PMID: 39475935 PMCID: PMC11524509 DOI: 10.1371/journal.pone.0305697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 06/04/2024] [Indexed: 11/02/2024] Open
Abstract
This study was designed as a randomized, placebo-controlled, double-blinded, cross-over trial performed to investigate the effects of a dietary supplement containing undenatured type II collagen (UCII®) and Boswellia Serrata on mobility, pain and joint metabolism in mild moderate osteoarthritis (OA) in dogs. A total of 60 dogs with mobility problems were evaluated and enrolled in the study. Seventeen of these dogs with mild/moderate OA were randomized to receive the product A (UCII® + Boswellia Serrata supplement-UCII®-BW) or product B (Placebo -PL), 1 chew per day for 8 weeks by oral route, and repeated in a crossover design after 4 weeks of washout period. All the subjects had veterinary evaluations during the trial and owners were requested to fill out a questionnaire on mobility impairment using the Liverpool Osteoarthritis in dogs scale (L.O.A.D.) at each time of the study. Objective tools were used to assess mobility, activity, and pain. Metabolomic analysis was performed on synovial fluid of most affected joint at the beginning and the end of the study. The results proved that UCII®+Boswellia serrata supplemented group over a period of eight weeks results in an improvement of mobility impairment, already at 4 weeks of administration, according to the owner´s evaluation. In contrast, its absence increased the risk of OA crisis and decreased the pain threshold on the most affected joint. Furthermore, the synovial fluid metabolic profile showed moderate differences between the beginning and the end of the supplementation period, with a particular influence associated to the time of UCII®-BW administration.
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Affiliation(s)
- Marzia Stabile
- Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (Di.Me.Pre-J), Università Degli Studi di Bari, Valenzano, Bari
| | - Laura Fracassi
- Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (Di.Me.Pre-J), Università Degli Studi di Bari, Valenzano, Bari
| | - Luca Lacitignola
- Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (Di.Me.Pre-J), Università Degli Studi di Bari, Valenzano, Bari
| | | | - Chiara Roberta Girelli
- Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (DiSTeBA), Università del Salento, Lecce, Italia
| | - Crescenza Calculli
- Dipartimento di Economia e Finanza, Università degli Studi di Bari, Bari, Italia
| | | | - Nunziata Ribecco
- Dipartimento di Economia e Finanza, Università degli Studi di Bari, Bari, Italia
| | - Antonio Crovace
- Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (Di.Me.Pre-J), Università Degli Studi di Bari, Valenzano, Bari
| | - Francesco Paolo Fanizzi
- Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (DiSTeBA), Università del Salento, Lecce, Italia
| | - Francesco Staffieri
- Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (Di.Me.Pre-J), Università Degli Studi di Bari, Valenzano, Bari
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Bruns Y, Schroers M, Steigmeier-Raith S, Waselau AC, Reese S, Meyer-Lindenberg A. Efficacy of a Single Injection of Stromal Vascular Fraction in Dogs with Elbow Osteoarthritis: A Clinical Prospective Study. Animals (Basel) 2024; 14:2803. [PMID: 39409752 PMCID: PMC11475770 DOI: 10.3390/ani14192803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/10/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
This study aimed to assess the efficacy of a single intra-articular injection of autologous stromal vascular fraction (SVF) in dogs with chronic lameness due to advanced elbow osteoarthritis (OA) that were unresponsive to conventional drug therapy. In this clinical, prospective, non-blinded, single-center study, twenty-three dogs received autologous SVF derived from falciform adipose tissue. Primary outcome measures over the six-month study period included clinical-orthopedic and radiographic examinations, objective gait analysis and validated owner questionnaires. In 19 of 23 joints, no progression of OA was visible radiographically. Peak vertical force improved significantly at three months and vertical impulse at six months after the injection compared to baseline. Over 33% of dogs demonstrated treatment-related improvements in lameness based on objective gait analysis. Owner questionnaires indicated significant improvement in clinical signs throughout the study period and 26% of dogs showed treatment-related improvements in pain scores according to the Canine Brief Pain Inventory. No side effects were reported. These findings suggest that autologous regenerative cell therapy may provide a promising treatment option for dogs with advanced OA that do not respond to conventional drug therapy. However, the treatment did not improve the clinical symptoms in all dogs, so it cannot be recommended for all patients.
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Affiliation(s)
- Yvonne Bruns
- Clinic of Small Animal Surgery and Reproduction, Ludwig-Maximilians-Universität München, 80539 Munich, Germany; (Y.B.); (S.S.-R.); (A.-C.W.); (A.M.-L.)
| | - Maike Schroers
- Clinic of Small Animal Surgery and Reproduction, Ludwig-Maximilians-Universität München, 80539 Munich, Germany; (Y.B.); (S.S.-R.); (A.-C.W.); (A.M.-L.)
| | - Stephanie Steigmeier-Raith
- Clinic of Small Animal Surgery and Reproduction, Ludwig-Maximilians-Universität München, 80539 Munich, Germany; (Y.B.); (S.S.-R.); (A.-C.W.); (A.M.-L.)
| | - Anja-Christina Waselau
- Clinic of Small Animal Surgery and Reproduction, Ludwig-Maximilians-Universität München, 80539 Munich, Germany; (Y.B.); (S.S.-R.); (A.-C.W.); (A.M.-L.)
| | - Sven Reese
- Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, Germany;
| | - Andrea Meyer-Lindenberg
- Clinic of Small Animal Surgery and Reproduction, Ludwig-Maximilians-Universität München, 80539 Munich, Germany; (Y.B.); (S.S.-R.); (A.-C.W.); (A.M.-L.)
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10
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Shentu CY, Wang HB, Peng X, Xu DC, Qian LN, Chen Y, Peng LH. Progress and Challenges of Topical Delivery Technologies Meditated Drug Therapy for Osteoarthritis. Int J Nanomedicine 2024; 19:8337-8352. [PMID: 39161359 PMCID: PMC11330747 DOI: 10.2147/ijn.s466437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 07/10/2024] [Indexed: 08/21/2024] Open
Abstract
Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed.
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Affiliation(s)
- Cheng-Yu Shentu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China
| | - Hao-Bin Wang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China
| | - Xiao Peng
- Jinhua Institute of Zhejiang University, Jinhua, Zhejiang, 321299, People’s Republic of China
| | - Dong-Chen Xu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China
| | - Li-Na Qian
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China
| | - Yong Chen
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China
- Jinhua Institute of Zhejiang University, Jinhua, Zhejiang, 321299, People’s Republic of China
| | - Li-Hua Peng
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China
- Jinhua Institute of Zhejiang University, Jinhua, Zhejiang, 321299, People’s Republic of China
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, People’s Republic of China
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11
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Carreira LM, Cota J, Alves J, Inácio F, Alexandre-Pires G, Azevedo P. A Pilot Study of the Clinical Effectiveness of a Single Intra-Articular Injection of Stanozolol in Canines with Knee Degenerative Joint Disease and Its Correlation with Serum Interleukin-1β Levels. Animals (Basel) 2024; 14:1351. [PMID: 38731355 PMCID: PMC11082967 DOI: 10.3390/ani14091351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/25/2024] [Accepted: 04/27/2024] [Indexed: 05/13/2024] Open
Abstract
Stanozolol shows promise as an anabolic and anti-catabolic agent for treating degenerative joint disease (DJD). This study assessed the clinical efficacy of a single intra-articular stanozolol injection in canine knees with DJD and its correlation with serum IL-1β levels. Thirty dogs (n = 30) were divided into a control group (CG, n = 10) and a study group (SG, n = 20) with DJD. Pain levels were assessed using the Brown query, and radiographs were taken at T0 and T3. IL-1β levels were quantified via ELISA. Apart from 2 patients, all showed reduced pain intensity, with 15 patients showing improvement at T1 and 3 patients at T2. A positive correlation (r = 0.84; p < 0.01) was found between pain level and IL-1β in 15 patients. No systemic effects were observed. Most patients (18/20) experienced reduced pain. This pilot study suggests stanozolol's potential in managing DJD in dogs. Further research is warranted to validate these findings and understand stanozolol's mechanism in DJD treatment.
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Affiliation(s)
- L. Miguel Carreira
- Anjos of Assis Veterinary Medicine Centre-CMVAA, Rua D.ª Francisca da Azambuja Nº9-9A, 2830-077 Barreiro, Portugal (P.A.)
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), Av. da Universidade Técnica, 1300-477 Lisbon, Portugal; (F.I.); (G.A.-P.)
- Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon (FMV/ULisboa), Av. da Universidade Técnica, 1300-477 Lisbon, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
- Faculty of American Laser Study Club—ALSC, Altamonte Springs, FL 32714, USA
| | - João Cota
- Anjos of Assis Veterinary Medicine Centre-CMVAA, Rua D.ª Francisca da Azambuja Nº9-9A, 2830-077 Barreiro, Portugal (P.A.)
| | - Joao Alves
- Divisão de Medicina Veterinária, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771 Lisbon, Portugal;
| | - Filipa Inácio
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), Av. da Universidade Técnica, 1300-477 Lisbon, Portugal; (F.I.); (G.A.-P.)
| | - Graça Alexandre-Pires
- Faculty of Veterinary Medicine, University of Lisbon (FMV/ULisboa), Av. da Universidade Técnica, 1300-477 Lisbon, Portugal; (F.I.); (G.A.-P.)
- Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon (FMV/ULisboa), Av. da Universidade Técnica, 1300-477 Lisbon, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Pedro Azevedo
- Anjos of Assis Veterinary Medicine Centre-CMVAA, Rua D.ª Francisca da Azambuja Nº9-9A, 2830-077 Barreiro, Portugal (P.A.)
- Faculty of American Laser Study Club—ALSC, Altamonte Springs, FL 32714, USA
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12
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Szotowska I, Ledwoń A. Antiviral Chemotherapy in Avian Medicine-A Review. Viruses 2024; 16:593. [PMID: 38675934 PMCID: PMC11054683 DOI: 10.3390/v16040593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 04/06/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
This review article describes the current knowledge about the use of antiviral chemotherapeutics in avian species, such as farm poultry and companion birds. Specific therapeutics are described in alphabetical order including classic antiviral drugs, such as acyclovir, abacavir, adefovir, amantadine, didanosine, entecavir, ganciclovir, interferon, lamivudine, penciclovir, famciclovir, oseltamivir, ribavirin, and zidovudine, repurposed drugs, such as ivermectin and nitazoxanide, which were originally used as antiparasitic drugs, and some others substances showing antiviral activity, such as ampligen, azo derivates, docosanol, fluoroarabinosylpyrimidine nucleosides, and novel peptides. Most of them have only been used for research purposes and are not widely used in clinical practice because of a lack of essential pharmacokinetic and safety data. Suggested future research directions are also highlighted.
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Affiliation(s)
- Ines Szotowska
- Department of Pathology and Veterinary Diagnostics, Warsaw University of Life Sciences, 02-776 Warsaw, Poland;
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13
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Norfolk M, Bielby J, Figueiredo Passos L, Reddon AR, Rendle M. Nutraceutical supplementation increases mobility in aged captive non-domesticated felids. Vet Rec 2024; 194:e3797. [PMID: 38379254 DOI: 10.1002/vetr.3797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 11/06/2023] [Accepted: 12/08/2023] [Indexed: 02/22/2024]
Abstract
BACKGROUND Musculoskeletal diseases (MSDs) are an increasing issue as the lifespan of captive animals increases. Extracts of green-lipped mussels have been linked to alleviation of MSDs in domestic carnivores. Understanding their efficacy in non-domestic felids could provide another tool to improve the welfare of aged individuals in collections. METHODS A within-subject study design quantified steps per minute in each of 18 cats of 13 species before and after the addition of a nutraceutical containing green-lipped mussel extract (Antinol) to their diets. The age structure of four commonly kept subspecies of non-domestic cats was quantified to provide a demographic context to the need for managing aged individuals. RESULTS Each of the 18 cats exhibited a higher number of steps per minute after the addition of Antinol to their diet. At the group level, a paired t-test showed that the step rate was significantly increased after the addition of Antinol to the diet. LIMITATIONS While our results showed a strong significant increase in step rate following Antinol supplementation, further studies that incorporate a placebo, more individuals and more detailed metrics of mobility would provide a more detailed evidence base for practitioners. CONCLUSION Nutraceuticals may yield benefits to aged individual felids, including species kept widely in European collections. Their use warrants further, detailed research in collections.
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Affiliation(s)
- Matthew Norfolk
- School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, UK
| | - Jon Bielby
- School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, UK
| | - Luiza Figueiredo Passos
- School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, UK
| | - Adam R Reddon
- School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, UK
| | - Matthew Rendle
- Association of Zoo and Exotic Veterinary Nurses, Market Harborough, UK
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14
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Liu DD, Zhao YC, Li HH, Yin LJ, Chen JQ, Liu G. Endoplasmic reticulum stress-related protein GRP78 and CHOP levels in synovial fluid correlate with disease progression of primary knee osteoarthritis: A cross-sectional study. J Appl Biomed 2024; 22:40-48. [PMID: 38505969 DOI: 10.32725/jab.2024.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 01/18/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.
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Affiliation(s)
| | | | - Hai-Hong Li
- Southern Medical University, The Third Affiliated Hospital, Department of Rehabilitation, 510630 Guangzhou, Guangdong Province, China
| | - Lian-Jun Yin
- Southern Medical University, The Third Affiliated Hospital, Department of Rehabilitation, 510630 Guangzhou, Guangdong Province, China
| | | | - Gang Liu
- Southern Medical University, Nanfang Hospital, Department of Rehabilitation Medicine, 510515 Guangzhou, Guangdong Province, China
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15
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Lopez AN, Bazer FW, Wu G. Functions and Metabolism of Amino Acids in Bones and Joints of Cats and Dogs. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1446:155-175. [PMID: 38625528 DOI: 10.1007/978-3-031-54192-6_7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/17/2024]
Abstract
The bone is a large and complex organ (12-15% of body weight) consisting of specialized connective tissues (bone matrix and bone marrow), whereas joints are composed of cartilage, tendons, ligaments, synovial joint capsules and membranes, and a synovial joint cavity filled with synovial fluid. Maintaining healthy bones and joints is a dynamic and complex process, as bone deposition (formation of new bone materials) and resorption (breakdown of the bone matrix to release calcium and phosphorus) are the continuous processes to determine bone balance. Bones are required for locomotion, protection of internal organs, and have endocrine functions to maintain mineral homeostasis. Joints are responsible for resisting mechanical stress/trauma, aiding in locomotion, and supporting the overall musculoskeletal system. Amino acids have multiple regulatory, compositional, metabolic, and functional roles in maintaining the health of bones and joints. Their disorders are prevalent in mammals and significantly reduce the quality of life. These abnormalities in companion animals, specifically cats and dogs, commonly lead to elective euthanasia due to the poor quality of life. Multiple disorders of bones and joints result from genetic predisposition and are heritable, but other factors such as nutrition, growth rate, trauma, and physical activity affect how the disorder manifests. Treatments for cats and dogs are primarily to slow the progression of these disorders and assist in pain management. Therapeutic supplements such as Cosequin and formulated diets rich in amino acids are used commonly as treatments for companion animals to reduce pain and slow the progression of those diseases. Also, amino acids (e.g., taurine, arginine, glycine, proline, and 4-hydroxyproline), and glucosamine reduce inflammation and pain in animals with bone and joint disorders. Gaining insight into how amino acids function in maintaining bone and joint health can aid in developing preventative diets and therapeutic supplementations of amino acids to improve the quality of life in companion animals.
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Affiliation(s)
- Arianna N Lopez
- Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA
| | - Fuller W Bazer
- Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA
| | - Guoyao Wu
- Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA.
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16
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Clark NL, Bates KT, Harris LK, Tomlinson AW, Murray JK, Comerford EJ. GenPup-M: A novel validated owner-reported clinical metrology instrument for detecting early mobility changes in dogs. PLoS One 2023; 18:e0291035. [PMID: 38150469 PMCID: PMC10752556 DOI: 10.1371/journal.pone.0291035] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 08/18/2023] [Indexed: 12/29/2023] Open
Abstract
OBJECTIVE To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity of a novel clinical metrology instrument ("GenPup-M") to detect canine mobility impairments. DESIGN Quantitative study. ANIMALS 62 dogs (31 with mobility impairments and 31 without mobility impairments). PROCEDURE The dogs' clinical history was obtained from owners and all dogs underwent a validated orthopaedic clinical examination. Mobility impairments were diagnosed in the mobility impaired group based on clinical history and orthopaedic examination. Owners were asked to complete GenPup-M along with a previously validated mobility questionnaire (Liverpool Osteoarthritis in Dogs (LOAD)) to identify construct validity. As a test of criterion validity, the correlation between instrument scores and the overall clinical examination scores, along with force-platform obtained peak vertical forces (PVF) were calculated. GenPup-M underwent internal consistency and factor analysis. Spatiotemporal parameters were calculated for dogs with/without mobility impairments to define the gait differences between these two groups. RESULTS Principal Component Analysis identified GenPup-M had two components with Eigenvalues >1 ("stiffness/ease of movement" and "willingness to be active/exercise"). Cronbach's α was used to test internal consistency of GenPup-M and was found to be "good" (0.87). There was a strong, positive correlation between GenPup-M and LOAD responses (r2 = 0.69, p<0.001) highlighting construct validity. Criterion validity was also shown when comparing GenPup-M to clinical examination scores (r2 = 0.74, p<0.001) and PVF (r2 = 0.43, p<0.001). Quantitative canine gait analysis showed that there were statistically significant differences between peak vertical forces (PVF) of mobility impaired and non-mobility impaired dogs (p<0.05). Analyses of PVF showed that non-mobility impaired dogs more evenly distributed their weight across all thoracic and pelvic limbs when compared to mobility impaired dogs. There were also consistent findings that mobility impaired dogs moved slower than non-mobility impaired dogs. CONCLUSION AND CLINICAL RELEVANCE GenPup-M is a clinical metrology instrument (CMI) that can be completed by dog owners to detect all mobility impairments, including those that are early in onset, indicating the versatility of GenPup-M to assess dogs with and without mobility impairments. Results of the study found that GenPup-M positively correlated with all three objective measures of canine mobility and consequently showed criterion and construct validity. Owner-reported CMIs such as GenPup-M allow non-invasive scoring systems which veterinary surgeons and owners can use to allow communication and longitudinal assessment of a dog's mobility. It is anticipated that GenPup-M will be used by owners at yearly vaccinations/health checks, allowing identification of any subtle mobility changes, and enabling early intervention.
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Affiliation(s)
- Natasha L. Clark
- Department of Musculoskeletal & Ageing Science, University of Liverpool, Liverpool, United Kingdom
| | - Karl T. Bates
- Department of Musculoskeletal & Ageing Science, University of Liverpool, Liverpool, United Kingdom
- Medical Research Council (MRC) and Versus Arthritis as part of the Medical Research Council Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Northumberland, United Kingdom
| | | | - Andrew W. Tomlinson
- Department of Small Animal Clinical Sciences, Small Animal Teaching Hospital, Neston, United Kingdom
| | - Jane K. Murray
- Department of Small Animal Clinical Sciences, Small Animal Teaching Hospital, Neston, United Kingdom
| | - Eithne J. Comerford
- Department of Musculoskeletal & Ageing Science, University of Liverpool, Liverpool, United Kingdom
- Medical Research Council (MRC) and Versus Arthritis as part of the Medical Research Council Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Northumberland, United Kingdom
- Dogs Trust, London, United Kingdom
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Yang Z, Jiang W, Xiong C, Shang J, Huang Y, Zhou X, Zhang S. Calcipotriol suppresses GPX4-mediated ferroptosis in OA chondrocytes by blocking the TGF-β1 pathway. Cytokine 2023; 171:156382. [PMID: 37782985 DOI: 10.1016/j.cyto.2023.156382] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 09/02/2023] [Accepted: 09/25/2023] [Indexed: 10/04/2023]
Abstract
Globally, tens of millions of individuals experience osteoarthritis (OA), a degenerative joint condition for which a definitive cure is currently lacking. This condition is characterized by joint inflammation and the progressive deterioration of articular cartilage. In this study, western blotting, quantitative reverse-transcription polymerase chain reaction, and immunofluorescence analysis were performed to elucidate the molecular mechanisms by which calcipotriol alleviates chondrocyte ferroptosis. The effect of calcipotriol on reactive oxygen species and lipid peroxidation levels in chondrocytes was assessed using dihydroethidium staining and the fluorescent dye BODIPY. To replicate OA, the destabilized medial meniscus model was employed, followed by the injection of calcipotriol into the knee articular cavity. Morphological analysis was conducted through hematoxylin and eosin staining, safranin O-Fast green staining, and micro-computed tomography analysis. Immunohistochemical analysis was performed to validate the effect of calcipotriol in vivo. Our results demonstrate that the expression of SOX9, col2a1, and Aggrecan, as well as MMP13 and ADAMTS5 protein expression levels, decrease upon treatment with calcipotriol in interleukin-1β stimulated chondrocytes. Despite these promising outcomes, the exact mechanism underlying calcipotriol's therapeutic effect on OA remains uncertain. We discovered that calcipotriol inhibits chondrocyte GPX4-mediated ferroptosis by suppressing the expression of transforming growth factor-β1. Furthermore, our study established an in vivo model of OA using rats with medial meniscus instability. Our experiments on rats with OA revealed that intra-articular calcipotriol injection significantly reduces cartilage degradation caused by the disease. Our findings suggest that calcipotriol can mitigate OA by impeding GPX4-mediated ferroptosis of chondrocytes, achieved through the suppression of the TGF-β1 pathway.
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Affiliation(s)
- Zhicheng Yang
- Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China
| | - Wei Jiang
- Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui 230022, China
| | - Chenwei Xiong
- Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China; Department of Orthopedics, Zhangjiajie People's Hospital, Zhangjiajie 427000, China
| | - JingJing Shang
- Department of Pharmacy, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China
| | - Yong Huang
- Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China
| | - Xindie Zhou
- Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China; Department of Orthopedics, Gonghe County Hospital of Traditional Chinese Medicine, Hainan Tibetan Autonomous Prefecture, Qinghai Province 811800, China.
| | - Su Zhang
- Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, 213000, China.
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18
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Clark N, Comerford E. An update on mobility assessment of dogs with musculoskeletal disease. J Small Anim Pract 2023; 64:599-610. [PMID: 37455329 DOI: 10.1111/jsap.13650] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 03/31/2023] [Accepted: 06/10/2023] [Indexed: 07/18/2023]
Abstract
Mobility impairments associated with musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, affect approximately 200,000 dogs annually and pose a notable challenge to canine health and welfare. Osteoarthritis causes the remodelling of synovial joints, alongside inflammation and impaired mechanical function which can be extremely debilitating. Secondary osteoarthritis commonly affects dogs and can be exacerbated by previous joint abnormalities, such as patellar luxation or cranial cruciate ligament rupture. Although musculoskeletal diseases can affect dogs of any age, the early subtle signs of gait abnormalities are perhaps missed by owners, thus, dogs may be in the latter stages of osteoarthritis progression when they are presented to veterinarians. Dogs showing subtle signs of gait abnormalities must be presented to veterinary practices for acute diagnosis to prevent long-term deterioration. Musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, are commonly diagnosed via visible radiographic changes. However, veterinarians can use a combination of subjective and objective clinical scoring systems, such as clinical metrology instruments and gait assessment in conjunction with radiography to aid their diagnosis and longitudinal monitoring of musculoskeletal diseases. These scoring systems may be more sensitive to earlier signs of mobility impairments in dogs, ultimately, promoting increased canine health and welfare by enabling pain reduction, improvement of muscle strength and preservation of joint function. Current canine mobility scoring systems available to veterinarians will be discussed in turn throughout this review for implementation into clinical practice.
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Affiliation(s)
- N Clark
- Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK
| | - E Comerford
- Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK
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19
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Gordon CL, Reeves SJ, Burchell RK, Thomson C, Gal A, Lopez‐Villalobos N, Webster NSL, Litster KM, Mitchell RAS. A blinded, placebo-controlled study on the clinical effects of vitamin E supplementation in dogs with osteoarthritis. J Vet Intern Med 2023; 37:1839-1847. [PMID: 37522795 PMCID: PMC10472994 DOI: 10.1111/jvim.16816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 07/05/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND Vitamin E has a positive effect in the management of osteoarthritis in humans, and in a previous study of dogs. It has been suggested to decrease C-reactive protein concentrations and liver enzyme activities in humans and animals. OBJECTIVE To assess the effect of vitamin E supplementation on lameness, pain, pain medication requirement, clinical pathology variables, and quality of life in large-breed dogs with naturally occurring osteoarthritis. ANIMALS Fifty-seven client-owned dogs with naturally occurring osteoarthritis. METHODS Dogs received either vitamin E or placebo for 90 days in a randomized, placebo-controlled, double-blinded, prospective clinical trial. Clinical lameness scores, pain medication requirements, and owner questionnaires were used to assess response to treatment every 30 days. Blood samples were collected at enrollment and at the end of the study period. RESULTS Vitamin E administration did not improve pain, lameness, or quality of life as assessed by owners and veterinarians. Vitamin E supplementation did not decrease the requirement for rescue pain relief. No changes in clinical pathology variables were observed after 90 days of vitamin E supplementation. Body weight was negatively associated with the lameness scores and requirement for rescue pain relief. CONCLUSION Vitamin E supplementation did not have any observable positive effects in dogs with naturally occurring osteoarthritis.
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Affiliation(s)
- Casey L. Gordon
- Department of SurgeryNorth Coast Veterinary SpecialistsSippy DownsQueenslandAustralia
| | - Samantha J. Reeves
- Department of MedicineNorth Coast Veterinary SpecialistsSippy DownsQueenslandAustralia
| | - Richard K. Burchell
- Department of MedicineNorth Coast Veterinary SpecialistsSippy DownsQueenslandAustralia
| | - Craig Thomson
- Department of SurgeryNorth Coast Veterinary SpecialistsSippy DownsQueenslandAustralia
| | - Arnon Gal
- Department of Veterinary Clinical MedicineUniversity of Illinois Urbana‐ChampaignUrbanaIllinoisUSA
| | | | | | - Kimberley M. Litster
- Department of SurgeryNorth Coast Veterinary SpecialistsSippy DownsQueenslandAustralia
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Zhao P, Ma G, Ma L. miR-181a-5p targets DDX3X to inhibit the progression of osteoarthritis via NF-ΚB signaling pathway. J Orthop Surg Res 2023; 18:606. [PMID: 37587519 PMCID: PMC10433630 DOI: 10.1186/s13018-023-04073-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 08/03/2023] [Indexed: 08/18/2023] Open
Abstract
Osteoarthritis (OA) is the most common age-related joint disease, characterized by chronic inflammation, progressive articular cartilage destruction and subchondral osteosclerosis. More and more evidence showed that microRNAs (miRNAs) play a key role in various diseases, but the specific mechanism of miRNAs in OA is not clear. The purpose of this study was to investigate the expression level and role of miR-181a-5p in OA and its related mechanism. Here we identified the key gene DEAD-box RNA helicase 3X (DDX3X) in the OA dataset by bioinformatics analysis. At the same time, miRNAs targeting DDX3X were screened, and miR-181a-5p was selected as the next research object. Then we used different concentrations of interleukin-1 beta (IL-1β)-induced in vitro model of arthritis, and found that IL-1β can stimulate cells to release nitric oxide. The expression levels of miR-181a-5p and DDX3X in mouse chondrocyte cell line ATDC5 induced by IL-1β at a concentration of 10ug/mL were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). IL-1β induced a decrease in the expression of miR-181a-5p and an increase in the expression of DDX3X in ATDC5 cells. mimic miR-181a-5p or inhibitor miR-181a-5p were transfected into ATDC5 cells, and the levels of inflammatory mediators in the cells were detected by enzyme-linked immunosorbent assay, and the results showed that miR-181a-5p could reduce the release of tumor necrosis factor-α, IL-1β, IL-6 and inducible nitric oxide nitric oxide synthase in a cellular model of arthritis. Luciferase reporter assays confirmed that the miR-181a-5p binding site was in the DDX3X gene 3'-untranslated region (3'-UTR), and DDX3X was negatively regulated by miR-181a-5p. Rescue assays confirmed that miR-181a-5p reduced the expression of DDX3X by targeting the 3'-UTR region of DDX3X, thereby reducing the release of inflammatory factors. Finally, in this paper, western blot was used to detect the mechanism of miR-181a-5p regulating OA. The results showed that interfering with the expression of miR-181a-5p could up-regulate the expression of DDX3X protein, increase the expression of nuclear factor- kappaB (NF-κB) related proteins, and reduce the inflammatory response of OA, thereby increasing the secretion of the matrix proteinases MMP-3 and MMP-13. Taken together, the results of the study suggested that miR-181a-5p may be a promising therapeutic target for the treatment of human OA.
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Affiliation(s)
- Peng Zhao
- Department of Rheumatology Immunology, 3201 Hospital, 783 Tianhan Avenue, Hantai District, Hanzhong, 723000, China.
| | - Guobin Ma
- Department of Rheumatology Immunology, 3201 Hospital, 783 Tianhan Avenue, Hantai District, Hanzhong, 723000, China
| | - Lintong Ma
- Department of Hematology, 3201 Hospital, Hanzhong, China
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21
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Bunnell NM, Weatherton L. Case report: Treatment of joint supplement toxicity resulting in acidemia, hyperglycemia, electrolyte derangements, and multiple organ dysfunction. Front Vet Sci 2023; 10:1141978. [PMID: 37456965 PMCID: PMC10347412 DOI: 10.3389/fvets.2023.1141978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 05/22/2023] [Indexed: 07/18/2023] Open
Abstract
Objective This case report describes a successful outcome in the treatment of a patient with joint supplement toxicity, which resulted in seizures, severe acidemia, hyperglycemia, hypernatremia, and multiple organ dysfunction. Previous case reports have been published, but this patient presented with different clinical signs and had additional biochemical abnormalities. Treatment modalities varied in this case report, and the patient was discharged sooner than those mentioned in previous reports. Case summary A 9-year-old spayed female Maltese mix was presented to a specialty hospital for joint supplement toxicity. Presenting clinical signs were vomiting and seizures. Primary biochemical abnormalities consisted of hypernatremia, hyperglycemia, acidemia, azotemia, and elevated liver enzymes. Treatment involved lowering the sodium quickly given the neurologic signs on presentation. Other treatment modalities consisted of sodium bicarbonate, insulin, and liver protectants. The patient responded quickly and was discharged after 3 days in the hospital. New or unique information provided This case report is different in that the patient was having seizures and was also hyperglycemic, in addition to the expected abnormalities of hypernatremia, acidemia, and multiple organ dysfunction. It also differs from prior reports in that the treatment of hypernatremia was managed as an acute process. This case report describes differing clinical signs, biochemical abnormalities, and treatment modalities that may have led to the discharge from the hospital in a shorter time.
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22
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Thoene M, Bejer-Olenska E, Wojtkiewicz J. The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review. Int J Mol Sci 2023; 24:ijms24108925. [PMID: 37240271 DOI: 10.3390/ijms24108925] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 04/27/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
Articular cartilage has very low metabolic activity. While minor injuries may be spontaneously repaired within the joint by chondrocytes, there is very little chance of a severely impaired joint regenerating itself when damaged. Therefore, any significant joint injury has little chance of spontaneously healing without some type of therapy. This article is a review that will examine the causes of osteoarthritis, both acute and chronic, and how it may be treated using traditional methods as well as with the latest stem cell technology. The latest regenerative therapy is discussed, including the use and potential risks of mesenchymal stem cells for tissue regeneration and implantation. Applications are then discussed for the treatment of OA in humans after using canine animal models. Since the most successful research models of OA were dogs, the first applications for treatment were veterinary. However, the treatment options have now advanced to the point where patients suffering from osteoarthritis may be treated with this technology. A survey of the literature was performed in order to determine the current state of stem cell technology being used in the treatment of osteoarthritis. Then, the stem cell technology was compared with traditional treatment options.
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Affiliation(s)
- Michael Thoene
- Department of Medical Biology, School of Public Health, University of Warmia and Mazury in Olsztyn, 10-561 Olsztyn, Poland
| | - Ewa Bejer-Olenska
- Department of Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
| | - Joanna Wojtkiewicz
- Department of Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
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23
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Gutierre E, Crosignani N, García‐Carnelli C, di Mateo A, Recchi L. A case report of CBD and THC as analgesic therapy in a cat with chronic osteoarthritic pain. Vet Med Sci 2023; 9:1021-1025. [PMID: 37002652 DOI: 10.1002/vms3.1057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2023] Open
Abstract
A 10-year-old mixed breed male cat presented with clinical signs related to chronic orthopaedic pain. Upon physical examination, pain was noted, based on the feline Musculoskeletal Pain Index (FMPI). An analgesic treatment with a full spectrum cannabis oil (1.8% CBD and 0.8% THC) was proposed for 30 days (0,5 mg/kg based on CBD). The FMPI scale score decreased more than 50%. This case reported a satisfactory outcome for the patient and the owner, although this medication could increase ALT. Given the paucity of literature published to date on the treatment of veterinary species with cannabis-based medications, further clinical and pharmacokinetic studies are necessary to study the safety and efficacy of its use.
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Affiliation(s)
- E Gutierre
- Facultad de Veterinaria Departamento de Clínicas y Hospital Veterinario Universidad de la República Montevideo Uruguay
| | - N Crosignani
- Facultad de Veterinaria Departamento de Clínicas y Hospital Veterinario Universidad de la República Montevideo Uruguay
| | - C García‐Carnelli
- Facultad de Química Departamento de Química Orgánica Universidad de la República Montevideo Uruguay
| | - A di Mateo
- Facultad de Veterinaria Departamento de Clínicas y Hospital Veterinario Universidad de la República Montevideo Uruguay
| | - L Recchi
- Facultad de Veterinaria Departamento de Clínicas y Hospital Veterinario Universidad de la República Montevideo Uruguay
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24
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Brondeel C, Weekers F, Van Hecke L, Depuydt E, Pauwelyn G, Verhoeven G, de Bouvré N, De Roeck P, Vandekerckhove P, Vanacker P, Bohm-Geerdink D, Daems R, Duchateau L, Saunders J, Samoy Y, Spaas J. Intravenous injection of equine mesenchymal stem cells in dogs with articular pain and lameness - A feasibility study. Stem Cells Dev 2023. [PMID: 36924281 DOI: 10.1089/scd.2022.0296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023] Open
Abstract
Osteoarthritis (OA) is a frequently occurring joint disorder in veterinary practice. Current treatments are focused on pain and inflammation; however, these are not able to reverse the pathological condition. Mesenchymal stem cells (MSCs) could provide an interesting alternative because of their immunomodulatory properties. The objective of this study was to evaluate the potential of a single intravenous injection of xenogeneic equine peripheral blood-derived MSCs (epbMSCs) as treatment for articular pain and lameness. Patients with chronic articular pain were intravenously injected with epbMSCs. They were evaluated at three time points (baseline and 2 follow-ups) by a veterinarian based on an orthopedic joint assessment and an owner canine brief pain inventory scoring. 35 Thirty-five dogs were included in the safety and efficacy evaluation of the study. Results showed that the ePB-MSC therapy was well tolerated with no treatment related adverse events and no increase in articular heat or pain. A significant improvement of lameness, range of motion, joint effusion, pain severity and interference scores was found 6 weeks post-treatment compared to baseline. This study demonstrates that future research on intravenous administration of epbMSCs is warranted to further explore its possible beneficial effects in dogs with chronic articular pain and lameness.
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Affiliation(s)
- Carlien Brondeel
- Ghent University, 26656, Department of Medical Imaging and Orthopedics of Domestic Animals, Merelbeke, Belgium;
| | | | - Lore Van Hecke
- Boehringer Ingelheim Animal Health, 72816, Veterinary medicine Belgium, Ghent, Belgium;
| | - Eva Depuydt
- Boehringer Ingelheim Animal Health, 72816, Veterinary Medicine Belgium, Evergem, Belgium;
| | - Glenn Pauwelyn
- Boehringer Ingelheim Animal Health, 72816, Veterinary Medicine Belgium, Evergem, Belgium;
| | - Geert Verhoeven
- Ghent University, 26656, Department of Medical Imaging and Orthopedics of Domestic Animals, Merelbeke, Belgium;
| | | | | | | | | | | | | | - Luc Duchateau
- Ghent University, 26656, Biometrics Research Center , Gent, Belgium;
| | - Jimmy Saunders
- Ghent University, 26656, Department of Medical Imaging and Orthopedics of Domestic Animals, Merelbeke, Belgium;
| | - Yves Samoy
- Ghent University, 26656, Department of Medical Imaging and Orthopedics of Domestic Animals, Merelbeke, Belgium;
| | - Jan Spaas
- Boehringer Ingelheim Animal Health, 72816, Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.,Ghent University, 26656, Department of Medical Imaging and Orthopedics of Domestic Animals, Gent, Belgium;
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25
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Derwich M, Górski B, Amm E, Pawłowska E. Oral Glucosamine in the Treatment of Temporomandibular Joint Osteoarthritis: A Systematic Review. Int J Mol Sci 2023; 24:4925. [PMID: 36902359 PMCID: PMC10003243 DOI: 10.3390/ijms24054925] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/18/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Temporomandibular disorders (TMDs) occur frequently within the general population and are the most common non-dental cause of orofacial pain. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease (DJD). There have been several different methods of treatment of TMJ OA listed, including pharmacotherapy among others. Due to its anti-aging, antioxidative, bacteriostatic, anti-inflammatory, immuno-stimulating, pro-anabolic and anti-catabolic properties, oral glucosamine seems to be a potentially very effective agent in the treatment of TMJ OA. The aim of this review was to critically assess the efficacy of oral glucosamine in the treatment of TMJ OA on the basis of the literature. PubMed and Scopus databases were analyzed with the keywords: (temporomandibular joints) AND ((disorders) OR (osteoarthritis)) AND (treatment) AND (glucosamine). After the screening of 50 results, eight studies have been included in this review. Oral glucosamine is one of the symptomatic slow-acting drugs for osteoarthritis. There is not enough scientific evidence to unambiguously confirm the clinical effectiveness of glucosamine supplements in the treatment of TMJ OA on the basis of the literature. The most important aspect affecting the clinical efficacy of oral glucosamine in the treatment of TMJ OA was the total administration time. Administration of oral glucosamine for a longer period of time, i.e., 3 months, led to a significant reduction in TMJ pain and a significant increase in maximum mouth opening. It also resulted in long-term anti-inflammatory effects within the TMJs. Further long-term, randomized, double-blind studies, with a unified methodology, ought to be performed to draw the general recommendations for the use of oral glucosamine in the treatment of TMJ OA.
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Affiliation(s)
- Marcin Derwich
- Department of Pediatric Dentistry, Medical University of Lodz, 90-419 Łódź, Poland
| | - Bartłomiej Górski
- Department of Periodontology and Oral Mucosa Diseases, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Elie Amm
- Department of Orthodontics and Dentofacial Orthopedics, Boston University, Boston, MA 02118, USA
| | - Elżbieta Pawłowska
- Department of Pediatric Dentistry, Medical University of Lodz, 90-419 Łódź, Poland
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26
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Zapata A, Fernández-Parra R. Management of Osteoarthritis and Joint Support Using Feed Supplements: A Scoping Review of Undenatured Type II Collagen and Boswellia serrata. Animals (Basel) 2023; 13:870. [PMID: 36899726 PMCID: PMC10000124 DOI: 10.3390/ani13050870] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/17/2023] [Accepted: 02/19/2023] [Indexed: 03/06/2023] Open
Abstract
In the multimodal management of osteoarthritis (OA) in recent decades, the use of feed supplements to maintain joint cartilage has been advocated. The aim of this scoping review is to present the results found in the veterinary literature on the use of undenatured type II collagen and Boswellia serrata in dogs, specifically its use in dogs with clinical signs of OA, healthy dogs after intense exercise or dogs with diseases that predispose the individual to OA. For this purpose, a literature review was carried out using the electronic databases PubMed, Web of Science and Google Scholar, from which a total of 26 records were included in this review: fourteen evaluating undenatured type II collagen, ten evaluating Boswellia serrata and two evaluating the combination of undenatured type II collagen and Boswellia serrata. The review of the records showed that undenatured type II collagen decreases the clinical signs associated with OA, improving the general clinical state with a reduction in the degree of lameness and increase in physical activity or mobility. Evaluating the response to supplementation with Boswellia serrata alone is complicated due to the limited publication of studies and variations in the purity and compositions of the products used, but in general terms, its combination with other feed supplements produces benefits by relieving pain and reducing the clinical signs of OA in dogs. The combination of both in the same product provides results similar to those obtained in undenatured type II collagen studies. In conclusion, undenatured type II collagen and Boswellia serrata are considered a valid option for the multimodal approach to the management of OA and for improving activity during intense exercise, but more studies are needed to conclude whether or not it prevents OA in dogs.
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Affiliation(s)
- Ana Zapata
- Hospital Veterinario de Referencia UCV, Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria y Ciencias Experimentales, Universidad Católica de Valencia San Vicente Mártir, 46018 Valencia, Spain
- Escuela de Doctorado, Programa de Doctorado en Ciencias de la Vida y del Medio Natural, Universidad Católica de Valencia San Vicente Mártir, 46002 Valencia, Spain
| | - Rocio Fernández-Parra
- Hospital Veterinario de Referencia UCV, Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria y Ciencias Experimentales, Universidad Católica de Valencia San Vicente Mártir, 46018 Valencia, Spain
- Departamento Medicina y Cirugía Animal, Facultad de Veterinaria y Ciencias Experimentales, Universidad Católica de Valencia San Vicente Mártir, 46002 Valencia, Spain
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27
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Kampa N, Kaenkangploo D, Jitpean S, Srithunyarat T, Seesupa S, Hoisang S, Yongvanit K, Kamlangchai P, Tuchpramuk P, Lascelles BDX. Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: A prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Front Vet Sci 2023; 10:1033188. [PMID: 36816197 PMCID: PMC9929184 DOI: 10.3389/fvets.2023.1033188] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 01/12/2023] [Indexed: 02/04/2023] Open
Abstract
Introduction Glucosamine hydrochloride and chondroitin sulfate are commonly used in dogs with OA, but evidence around efficacy is mixed. This study evaluated the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the alleviation of canine hip OA pain. This was a prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Methods Seventy-five owned pet dogs with hip OA were assigned randomly into five treatment groups: PCSO-524, Glucosamine and chondroitin sulfate, EAB-277, carprofen, and Placebo (sunflower oil). Peak vertical force (PVF) and subjective orthopedic assessment scores (OAS) were evaluated before treatment (week 0), and at weeks 2, 4, and 6 during treatment. Results At week 2, the carprofen group showed a significant increase in PVF (3.14 ± 5.33; mean ± SD). After 4 weeks, the increases in PVF of the PCSO-524 (3.90 ± 3.52), EAB-277 (4.17 ± 4.94), and carprofen (3.08 ± 5.87) groups were significant, and significantly greater than placebo (0.08 ± 1.90) and glucosamine (-0.05 ± 6.34) groups. After 6 weeks, the change of PVF in the PCSO-524 (4.14 ± 4.65), EAB-277 (4.45 ± 4.23), and carprofen (4.21 ± 6.52) groups were significant and significantly higher than the placebo group (-0.33 ± 3.65). The change in PVF in the glucosamine group (1.08 ± 5.49) lay between the placebo group and the other treatment groups. The OAS did not show any significant change in any group. Discussion PCSO-524 and EAB-277, but not glucosamine/chondroitin, resulted in significant improvements in PVF from baseline after 4 weeks, and 6 weeks, and to a similar degree to that seen with carprofen.
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Affiliation(s)
- Naruepon Kampa
- Division of Surgery, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Duangdaun Kaenkangploo
- Division of Surgery, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Supranee Jitpean
- Division of Surgery, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Thanikul Srithunyarat
- Division of Surgery, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Suvaluk Seesupa
- Division of Surgery, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Somphong Hoisang
- Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Karn Yongvanit
- Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Phanthit Kamlangchai
- Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand
| | | | - B. Duncan X. Lascelles
- Translational Research in Pain Program, Comparative Pain Research and Education Centre, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States
- Center for Translational Pain Research, Department of Anesthesiology, Duke University, Durham, NC, United States
- Thurston Arthritis Center, UNC, Chapel Hill, NC, United States
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28
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Shim H, Lee J, Choi S, Kim J, Jeong J, Cho C, Kim H, Kim JI, Kim J, Eom K. Deep learning-based diagnosis of stifle joint diseases in dogs. Vet Radiol Ultrasound 2023; 64:113-122. [PMID: 36444910 DOI: 10.1111/vru.13181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 08/24/2022] [Accepted: 08/24/2022] [Indexed: 12/03/2022] Open
Abstract
In this retrospective, analytical study, we developed a deep learning-based diagnostic model that can be applied to canine stifle joint diseases and compared its accuracy with that achieved by veterinarians to verify its potential as a reliable diagnostic method. A total of 2382 radiographs of the canine stifle joint from cooperative animal hospitals were included in a dataset. Stifle joint regions were extracted from the original images using the faster region-based convolutional neural network (R-CNN) model, and the object detection accuracy was evaluated. Four radiographic findings: patellar deviation, drawer sign, osteophyte formation, and joint effusion, were observed in the stifle joint and used to train a residual network (ResNet) classification model. Implant and growth plate groups were analyzed to compare the classification accuracy against the total dataset. All deep learning-based classification models achieved target accuracies exceeding 80%, which is comparable to or slightly less than those achieved by veterinarians. However, in the case of drawer signs, further research is necessary to improve the low sensitivity of the model. When the implant group was excluded, the classification accuracy significantly improved, indicating that the implant acted as a distraction. These results indicate that deep learning-based diagnoses can be expected to become useful diagnostic models in veterinary medicine.
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Affiliation(s)
- Hyesoo Shim
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Jongmo Lee
- Department of Computer Science and Engineering, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Seunghoon Choi
- Department of Computer Science and Engineering, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Jayon Kim
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Jeongyun Jeong
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Changhyun Cho
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Hyungseok Kim
- Department of Computer Science and Engineering, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Jee-In Kim
- Department of Computer Science and Engineering, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Jaehwan Kim
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
| | - Kidong Eom
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul, Republic of Korea
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29
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Gabriele V, Bisanzio D, Riva A, Meineri G, Adami R, Martello E. Long-term effects of a diet supplement containing Cannabis sativa oil and Boswellia serrata in dogs with osteoarthritis following physiotherapy treatments: a randomised, placebo-controlled and double-blind clinical trial. Nat Prod Res 2022; 37:1782-1786. [PMID: 36067506 DOI: 10.1080/14786419.2022.2119967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Dogs are commonly affected by Osteoarthritis (OA). Different approaches can be used to alleviate animals' symptoms. In this randomised, placebo-controlled and double-blind clinical trial, we performed a three months follow-up study assessing the efficacy of a food supplement containing natural ingredients (Cannabis sativa oil, Boswellia serrata Roxb. Phytosome® and Zingiber officinale extract) in dogs with OA after the interruption of physiotherapy that was performed during the previous three months. Inflammation and oxidative stress were reduced in the treated group (higher glutathione (GSH) and lower C-reactive protein [CRP] levels in blood) as well as chronic pain.
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Affiliation(s)
| | | | | | - Giorgia Meineri
- Department of Veterinary Sciences, University of Turin, Grugliasco, Italy
| | | | - Elisa Martello
- Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
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30
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Matsubara L, Teixeira L, Mesquita L, Landeira-Fernandez J, Anunciação L, Luna S. Psychometric properties of the Brazilian version of the Canine Brief Pain Inventory (CBPI) for dogs with clinical signs of osteoarthritis and preliminary evidence of its clinical utility. ARQ BRAS MED VET ZOO 2022. [DOI: 10.1590/1678-4162-12542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
ABSTRACT This study aimed to determine the psychometric properties and clinical use of the Brazilian version of the Canine Brief Pain Inventory (CBPI) in dogs with hip dysplasia (HD). Forty-three dogs with HD and 16 clinically normal dogs were enrolled. The HD dogs were treated daily with 4.4mg/kg carprofen (GT = 21) or placebo (GP = 19), for four weeks. Owners completed the CBPI at two weeks (W-2) and immediately before the start of the treatment (W0), two (W2) and four (W4) weeks during treatment, and two weeks (W6) after the end of treatment. The internal structure was accessed, and the Cronbach’s alpha coefficient was 0.97, indicating the high internal consistency of the instrument. Principal Component Analysis (PCA) suggested the retention of one component, which accounted for 78% of the variability. The ROC curve analysis concluded that the score 3 has an excellent performance to discriminate between normal and possible HD dogs (AUC of 0.973). There was no difference between dogs treated with carprofen versus placebo. The instrument in Portuguese showed construct and criterion validity and reliability to be used in dogs with HD.
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Affiliation(s)
| | | | | | | | - L. Anunciação
- Pontificia Universidade Católica do Rio de Janeiro, Brazil
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31
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Effects of Intra-Articular Autologous Adipose Micrograft for the Treatment of Osteoarthritis in Dogs: A Prospective, Randomized, Controlled Study. Animals (Basel) 2022; 12:ani12141844. [PMID: 35883392 PMCID: PMC9311928 DOI: 10.3390/ani12141844] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 07/14/2022] [Indexed: 12/12/2022] Open
Abstract
The purpose of this study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs with spontaneous osteoarthritis (OA) in comparison with hyaluronic acid (HA), the standard intra-articular treatment. Specifically, it clinically evaluated pain and lameness, the radiographic progression of osteoarthritis, and synovial fluid inflammation. This was a prospective, single-center, parallel-group, randomized, controlled, in vivo clinical study. Participants (n = 40) received either a single intra-articular injection of microfragmented adipose tissue or a single intra-articular injection of HA (1:1). Clinical outcomes were determined using a specialistic clinician assessment obtained by the completion of a specific clinical form based on the Vesseur modified lameness classification system, a pain evaluation using the Visual Analogue Scale (VAS), the measurement of the range of motion (ROM) of the affected joint, limb circumference, and the owners' score evaluation using the Canine Brief Pain Inventory (CBPI) for up to 6 months after the time of injection. Patients underwent a radiographic examination to establish the degree of OA in the affected joint, and synovial fluid samples were collected to assess the biochemical environment of the joint and evaluate and quantify the cellular population and the presence of three specific inflammation biomarkers for up to 60 days. The results of this study suggest that microfragmented autologous adipose tissue is safe and can effectively relieve pain and improve function in dogs with spontaneous articular OA. This one-step procedure is simple, timesaving, cost-effective, minimally invasive, and eliminates the need for complex and time-intensive cell culture processing. Furthermore, the clinical evidence and cytological results suggest better long-term pain control, resulting in an improvement in joint function, compared to HA treatment. The canine spontaneous OA model could play a key role in developing successful treatments for human medicine.
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32
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Wright A, Amodie DM, Cernicchiaro N, Lascelles BDX, Pavlock AM, Roberts C, Bartram DJ. Identification of canine osteoarthritis using an owner-reported questionnaire and treatment monitoring using functional mobility tests. J Small Anim Pract 2022; 63:609-618. [PMID: 35385129 PMCID: PMC9543207 DOI: 10.1111/jsap.13500] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 02/10/2022] [Accepted: 03/11/2022] [Indexed: 12/14/2022]
Abstract
Objectives To investigate the diagnostic value of an owner‐completed canine osteoarthritis screening checklist to help identify previously undiagnosed osteoarthritis cases, and assess their response to carprofen treatment by monitoring pain and functional mobility. Materials and Methods Dogs (n=500) whose owners reported ≥1 positive response to the osteoarthritis checklist were examined to identify dogs with previously undiagnosed osteoarthritis. Eligible dogs (n=133) were evaluated for pain and video mobility analysis by Helsinki Chronic Pain Index and visual analogue scale scores, respectively, following carprofen treatment, administered for 30 days (n=95) or up to 120 days (n=38). Dogs were filmed at clinics performing activities (walking, jogging, sitting/lying, walking up and down stairs), and scored at days 0, 30 and 120 using visual analogue scale by an independent blinded expert. Results A diagnosis of osteoarthritis was confirmed by a veterinarian in 38% (188 of 500) of dogs. Balance of sensitivity and specificity across the original group of nine screening questions was optimised to approximately 88 and 71%, respectively, after elimination of three questions. Pain measured by Helsinki Chronic Pain Index and functional mobility improved over time in response to treatment with carprofen. Mean ability scores for activities significantly improved between days 0 and 30 for walking, jogging, sitting/lying and walking down stairs, and days 0 and 120 for sitting/lying and walking up stairs. Clinical Significance More osteoarthritis cases were identified in study dogs than previous prevalence estimates, indicating the screening checklist's potential to help identify for further evaluation cases that could otherwise remain undiagnosed. Improvements in function were demonstrated after carprofen treatment.
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Affiliation(s)
- A Wright
- Outcomes Research, Zoetis Inc., Parsippany, New Jersey, 07054, USA
| | - D M Amodie
- Outcomes Research, Zoetis Inc., Parsippany, New Jersey, 07054, USA
| | - N Cernicchiaro
- Center for Outcomes Research and Epidemiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, 66506, USA
| | - B D X Lascelles
- Comparative Pain Research and Education Centre & Translational Research in Pain Program, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, 27606, USA
| | - A M Pavlock
- AMP Research Solutions, Parker Ford, Pennsylvania, 19457, USA
| | - C Roberts
- vHive, School of Veterinary Medicine, University of Surrey, Guildford, GU2 7AL, UK
| | - D J Bartram
- Outcomes Research, Zoetis Inc., Parsippany, New Jersey, 07054, USA
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Hoffman JM, Tolbert MK, Promislow DEL. Demographic factors associated with joint supplement use in dogs from the Dog Aging Project. Front Vet Sci 2022; 9:906521. [PMID: 35958315 PMCID: PMC9361857 DOI: 10.3389/fvets.2022.906521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/04/2022] [Indexed: 01/29/2023] Open
Abstract
Osteoarthritis (OA) is one of the most prevalent age-related chronic conditions that afflict companion dogs, and multiple joint supplements are available to prevent or treat OA, though the efficacy of these treatments is controversial. While the demographic factors that are associated with OA diagnosis are well established, the factors that are associated with joint supplement use are not as well studied. Using data collected from the Dog Aging Project, we analyzed owner survey responses regarding joint supplement administration and OA diagnosis for 26,951 adult dogs. In this cross-sectional analysis, logistic regression models and odds-ratios (OR) were employed to determine demographic factors of dogs and their owners that were associated with joint supplement administration. Forty percent of adult dogs in our population were given some type of joint supplement. Perhaps not surprisingly, dogs of older age, larger size, and those that were ever overweight were more likely to receive a joint supplement. Younger owner age, urban living, owner education, and feeding commercial dry food were associated with a reduced likelihood of administration of joint supplements to dogs. Interestingly, mixed breed dogs were also less likely to be administered a joint supplement (OR: 0.73). Dogs with a clinical diagnosis of OA were more likely to receive a joint supplement than those without a reported OA diagnosis (OR: 3.82). Neutered dogs were more likely to have a diagnosis of OA, even after controlling for other demographic factors, yet their prevalence of joint supplement administration was the same as intact dogs. Overall, joint supplement use appears to be high in our large population of dogs in the United States. Prospective studies are needed to determine if joint supplements are more commonly administered as a preventative for OA or after an OA clinical diagnosis.
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Affiliation(s)
- Jessica M Hoffman
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - M Katherine Tolbert
- Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States
| | - Daniel E L Promislow
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States.,Department of Biology, University of Washington, Seattle, WA, United States
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Voga M, Majdic G. Articular Cartilage Regeneration in Veterinary Medicine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1401:23-55. [DOI: 10.1007/5584_2022_717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Kane LP, Cook JL, Archibald KE, Suedmeyer WK, Langan JN, Adkesson MJ. Complications associated with total hip arthroplasty in four large nondomestic felids. Am J Vet Res 2021; 83:180-187. [PMID: 34941567 DOI: 10.2460/ajvr.21.10.0161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
CASE DESCRIPTION A 9-year-old 37-kg sexually intact male snow leopard (Panthera uncia) with no history of lameness but radiographic evidence of right femoral subluxation and flattening of both femoral heads, 2 juvenile (< 1 year old) 25-kg sexually intact male cheetahs (Acinoynx jubatus) with unilateral hind limb lameness resulting from trauma, and an 11-year-old 110-kg sexually intact female Amur tiger (Panthera tigris altaica) with a 2-year history of left hip joint osteoarthritis were examined. CLINICAL FINDINGS No clinically relevant clinical findings other than hip joint problems were identified. All 4 felids underwent staged bilateral (snow leopard) or unilateral (cheetahs and tiger [Panthera tigris]) total hip arthroplasty (THA). TREATMENT AND OUTCOME In the snow leopard, both femoral THA components were found to be luxated 1 year after surgery. Treatment consisted of autogenous corticocancellous rib graft augmentation of the dorsal acetabular rims and synthetic suture capsulorrhaphies. The snow leopard lived for an additional 4 years with no additional THA-related complications. In the other 3 animals, catastrophic complications (luxation in the cheetahs and femoral fracture in the tiger) occurred shortly after THA. The THA implants were removed, and excision arthroplasty was performed. Long-term outcomes were good in all 3. CLINICAL RELEVANCE Findings underscore the challenges associated with THA in large nondomestic felids. Given the high risk for early catastrophic failure as a result of luxation or fracture, plans must be made and resources must be available in case revision surgery or implant removal with excision arthroplasty becomes necessary.
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Affiliation(s)
- Lauren P Kane
- 1Chicago Zoological Society, Brookfield Zoo, Brookfield, IL.,2Illinois Zoological and Aquatic Animal Residency Program, Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL
| | - James L Cook
- 3Missouri Orthopaedic Institute, University of Missouri, Columbia, MO
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Zhang H, Lu Y, Wu B, Xia F. Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1. Bioengineered 2021; 12:9641-9654. [PMID: 34821196 PMCID: PMC8810004 DOI: 10.1080/21655979.2021.1974806] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
Semaphorin 3A (SEMA3A) and its receptor neuropilin-1 (NRP-1) are expressed low in chondrocytes under stress, and overexpressing SEMA3A reduces pro-inflammatory cytokine release. This study was aimed at exploring whether SEMA3A participates in lipopolysaccharide (LPS)-induced chondrocyte inflammation, apoptosis and extracellular matrix (ECM) degradation. SEMA3A and NRP-1 expression in LPS-induced ATDC5 cells was determined with RT-qPCR and western blotting. Following stimulation with LPS in the absence or presence of SEMA3A overexpression, the viability of ATDC5 cells was observed through CCK-8 assay. RT-qPCR and western blot were performed to detect the expression of pro-inflammatory cytokines. ATDC5 cell apoptosis was observed through TUNEL, and apoptosis-related proteins were assayed. Expression of ECM-related proteins was measured by RT-qPCR and western blotting. Additionally, the binding of SEMA3A to NRP-1 was verified by co-immunoprecipitation. After interference with NRP-1, cell viability, inflammation and ECM degradation were examined in LPS-induced ATDC5 cells with SEMA3A overexpression. Results revealed that SEMA3A expression in ATDC5 cells decreased following stimulation with LPS. Overexpressing SEMA3A improved cell viability and reduced the inflammatory injury of LPS-stimulated ATDC5 cells. Moreover, SEMA3A overexpression alleviated LPS-induced apoptosis and ECM degradation of ATDC5 chondrocytes. SEMA3A and NRP-1 bound to each other in ATDC5 cells. NRP-1 interference crippled the ameliorative effect of SEMA3A overexpression on LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. To conclude, SEMA3A binds to NRP-1, mitigating LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. This study elucidated the role of SEMA3A in osteoarthritis and illustrated its action mechanism involving NRP-1.
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Affiliation(s)
- Huiyu Zhang
- Department of Hand Surgery, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, China
| | - Yue Lu
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - BingBing Wu
- Department of Hand Surgery, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, China
| | - Fei Xia
- Department of Hand Surgery, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, China
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De Francesco F, Riccio V, Biswas R, Busato A, Di Bella C, Serri E, Sbarbati A, Zavan B, Riccio M, Palumbo Piccionello A. In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions. Animals (Basel) 2021; 11:ani11113231. [PMID: 34827964 PMCID: PMC8614580 DOI: 10.3390/ani11113231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/03/2021] [Accepted: 11/10/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Mesenchymal stem cells are located in bone marrow, adipose tissue, synovial membrane, and muscular tissue. They have an immunosuppressive, anti-inflammatory, and antifibrotic effect. Tissue engineering considers the usage of mesenchymal stem cells as a possible option for regenerating tissues, with respect to bone and cartilage, due to their ability to differentiate into multiple cytotypes (including chondrocytes and osteoblasts). Herein, we characterize a non-invasive solution based on Rigenera® technology, a mechanical disaggregation method able to produce autologous adipose tissue-derived micrografts which are analogous to adipose-derived stem cells. Abstract Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses.
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Affiliation(s)
- Francesco De Francesco
- Hand Surgery Unit, Department of Plastic and Reconstructive Surgery, Azienda ‘Ospedali Riuniti di Ancona’, 60126 Ancona, Italy;
- Correspondence: ; Tel.: +39-071-5963945; Fax: +39-071-5965297
| | - Valentina Riccio
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Matelica, Italy; (V.R.); (C.D.B.); (E.S.); (A.P.P.)
| | - Reetuparna Biswas
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, 37179 Verona, Italy; (R.B.); (A.B.); (A.S.)
| | - Alice Busato
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, 37179 Verona, Italy; (R.B.); (A.B.); (A.S.)
| | - Caterina Di Bella
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Matelica, Italy; (V.R.); (C.D.B.); (E.S.); (A.P.P.)
| | - Evelina Serri
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Matelica, Italy; (V.R.); (C.D.B.); (E.S.); (A.P.P.)
| | - Andrea Sbarbati
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, 37179 Verona, Italy; (R.B.); (A.B.); (A.S.)
| | - Barbara Zavan
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy;
| | - Michele Riccio
- Hand Surgery Unit, Department of Plastic and Reconstructive Surgery, Azienda ‘Ospedali Riuniti di Ancona’, 60126 Ancona, Italy;
| | - Angela Palumbo Piccionello
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Matelica, Italy; (V.R.); (C.D.B.); (E.S.); (A.P.P.)
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Li J, Zhang Z, Qiu J, Huang X. 8-Methoxypsoralen has Anti-inflammatory and Antioxidant Roles in Osteoarthritis Through SIRT1/NF-κB Pathway. Front Pharmacol 2021; 12:692424. [PMID: 34552480 PMCID: PMC8450503 DOI: 10.3389/fphar.2021.692424] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 08/12/2021] [Indexed: 12/22/2022] Open
Abstract
Osteoarthritis (OA) is mainly manifested by joint pain, stiffness and mobility disorder, which is the main cause of pain and disability in middle-aged and elderly people. In this study, we aimed to explore the role and mechanism of 8-Methoxypsoralen (8-MOP) in the OA model both in vitro and in vivo. The rat chondrocytes were treated with IL-1β, and the proliferation, apoptosis, inflammatory reactions and oxidative stress responses were determined after treatment with different concentrations of 8-MOP. Real-time quantitative polymerase chain reaction (qRT-PCR) and/or Western blot were implemented to check the AMPK/SIRT1/NF-κB expression in chondrocytes. The NF-κB activity was determined by dual luciferase experiment. The pain threshold of OA rat model dealt with 8-MOP and/or the SIRT1 inhibitor EX527 was measured. Our results revealed that 8-MOP evidently reduced IL-1β-mediated apoptosis and inhibition of proliferation, and mitigated the expression of inflammatory cytokines and oxidative stress factors in chondrocytes. Additionally, 8-MOP promoted phosphorylated level of AMPKα, enhanced SIRT1 expression and inhibited the phosphorylation of NF-κB. After treatment with EX527, 8-MOP-mediated protective effects on chondrocytes were mostly reversed. In vivo, 8-MOP obviously improved the pain threshold in the OA rat model and reduced the injury and apoptosis of chondrocytes in the joints. In addition, 8-MOP relieved inflammatory and oxidative stress responses in the articular cartilage via enhancing SIRT1 and repressing NF-κB activation. After the treatment with EX527, the 8-MOP-mediated protective effects were distinctly weakened. In summary, our study testified that 8-MOP alleviates pain, inflammatory and oxidative stress responses in OA rats through the SIRT1/NF-κB pathway, which is expected to become a new reagent for clinical treatment of OA.
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Affiliation(s)
- Jichao Li
- The Third Department of Knee Injury, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Luoyang, China
| | - Zeng Zhang
- Zhengzhou Orthopedic Hospital, Zhengzhou, China
| | - Jinan Qiu
- The Third Department of Knee Injury, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Luoyang, China
| | - Xiaohan Huang
- The Third Department of Knee Injury, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Luoyang, China
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Mejia S, Duerr FM, Griffenhagen G, McGrath S. Evaluation of the Effect of Cannabidiol on Naturally Occurring Osteoarthritis-Associated Pain: A Pilot Study in Dogs. J Am Anim Hosp Assoc 2021; 57:81-90. [PMID: 33450016 DOI: 10.5326/jaaha-ms-7119] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/04/2020] [Indexed: 11/11/2022]
Abstract
The objective of this study was to provide preliminary data describing the safety and effect of cannabidiol (CBD) for symptom relief of canine osteoarthritis-associated pain in a clinical setting using objective outcome measures. Twenty-three client-owned dogs with naturally occurring osteoarthritis of appendicular joints completed this prospective, double-blinded, crossover, placebo-controlled study. Baseline data were acquired for 4 wk, followed by random allocation to either placebo or CBD treatment for 6 wk, followed by 6 wk with the opposite treatment. Outcome measures included objective gait analysis, activity counts (via accelerometry) and clinical metrology instruments. There were no differences noted between groups at any time point for any of the recorded outcome measures. Adverse events associated with CBD administration included elevation in liver enzymes (n = 14) and vomiting (n = 2).
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Xu H, Zhang J, Shi X, Li X, Zheng C. NF-κB inducible miR-30b-5p aggravates joint pain and loss of articular cartilage via targeting SIRT1-FoxO3a-mediated NLRP3 inflammasome. Aging (Albany NY) 2021; 13:20774-20792. [PMID: 34455406 PMCID: PMC8436920 DOI: 10.18632/aging.203466] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 06/23/2021] [Indexed: 02/07/2023]
Abstract
MicroRNAs (miRNAs) contribute to osteoarthritis (OA) development. Nevertheless, the function and mechanism of miR-30b-5p in OA are unclear. In the present article, we gauged the miR-30b-5p level in OA patients and analyzed its correlation with OA stages. Then, we conducted in-vivo and in-vitro gain-of-function assays to determine the function of miR-30b-5p, silent information regulator 2 homolog 1 (SIRT1) and Fox. Cell counting Kit-8 (CCK-8) assay, BrdU assay and flow cytometry were utilized to gauge cell viability and apoptosis of human chondrocyte (HC-A). The targeting association between miR-30b-5p and SIRT1 was validated through the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment. The results signified that miR-30b-5p was up-regulated in OA patients, OA rats and interleukin-1β (IL-1β)-induced chondrocytes. The higher miR-30b-5p expression brought about progressive stages of OA patients and enhanced levels of pro-inflammatory mediators in the synovial fluid. Functionally, overexpressing miR-30b-5p hampered cell viability, aggravated chondrocyte apoptosis and NLRP3 inflammasome activation induced by IL-1β, while down-regulating miR-30b-5p exerted the reverse effects. The in-vivo experiment exhibited that down-regulating miR-30b-5p improved joint pain and loss of articular cartilage in the rats with restrained inflammation and NLRP3 inflammasome activation. Mechanistically, miR-30b-5p targeted the 3'-non-translated region (3'UTR) of SIRT1, and miR-30b-5p was inducible with NF-κB phosphorylation enhancement. Overexpressing SIRT1 or inhibiting NF-κB relieved miR-30b-5p-induced apoptosis and NLRP3 inflammasome activation by promoting FoxO3a, while down-regulating SIRT1 or FoxO3a reversed miR-30b-5p-in-induced anti-inflammatory and apoptosis-suppressive effects. Collectively, NF-κB-induced miR-30b-5p modulates chondrocyte apoptosis and OA progression by regulating the SIRT1-FoxO3a-mediated NLRP3 inflammasome.
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Affiliation(s)
- Haiting Xu
- Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
| | - Jie Zhang
- Department of Stomatology, Linyi People's Hospital, Linyi 276003, Shandong, China
| | - Xiaoming Shi
- Department of Stomatology, Linyi People's Hospital, Linyi 276003, Shandong, China
| | - Xiaoyang Li
- Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
| | - Chao Zheng
- Department of Reparative and Reconstructive Surgery, Linyi People's Hospital, Linyi 276003, Shandong, China
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Prządka P, Buczak K, Frejlich E, Gąsior L, Suliga K, Kiełbowicz Z. The Role of Mesenchymal Stem Cells (MSCs) in Veterinary Medicine and Their Use in Musculoskeletal Disorders. Biomolecules 2021; 11:1141. [PMID: 34439807 PMCID: PMC8391453 DOI: 10.3390/biom11081141] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/27/2021] [Accepted: 07/30/2021] [Indexed: 12/11/2022] Open
Abstract
Regenerative medicine is a dynamically developing field of human and veterinary medicine. The animal model was most commonly used for mesenchymal stem cells (MSCs) treatment in experimental and preclinical studies with a satisfactory therapeutic effect. Year by year, the need for alternative treatments in veterinary medicine is increasing, and other applications for promising MSCs and their biological derivatives are constantly being sought. There is also an increase in demand for other methods of treating disease states, of which the classical treatment methods did not bring the desired results. Cell therapy can be a realistic option for treating human and animal diseases in the near future and therefore additional research is needed to optimize cell origins, numbers, or application methods in order to standardize the treatment process and assess its effects. The aim of the following work was to summarize available knowledge about stem cells in veterinary medicine and their possible application in the treatment of chosen musculoskeletal disorders in dogs and horses.
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Affiliation(s)
- Przemysław Prządka
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
| | - Krzysztof Buczak
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
| | - Ewelina Frejlich
- 2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Ludwika Gąsior
- Vets & Pets Veterinary Clinic, Zakladowa 11N, 50-231 Wroclaw, Poland;
| | - Kamil Suliga
- Student Veterinary Surgical Society “LANCET”, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwaldzki 51, 50-366 Wroclaw, Poland;
| | - Zdzisław Kiełbowicz
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
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Dinwiddie EV, Rendahl A, Veytsman S, Ragetly G, Lynch AC, Miniter B, Ben-Amotz R. Evaluation of post-operative complications, outcome, and long-term owner satisfaction of elbow arthrodesis (EA) in 22 dogs. PLoS One 2021; 16:e0255388. [PMID: 34329353 PMCID: PMC8323925 DOI: 10.1371/journal.pone.0255388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 07/16/2021] [Indexed: 11/19/2022] Open
Abstract
The objective of this study was to report post-operative complications and outcomes in canines undergoing elbow arthrodesis (EA) with fixation techniques including bone plate fixation with a non-locking dynamic compression plate (DCP), bone plate fixation with a locking plate (LCP), and external skeletal fixator (ESF). Medical records of twenty-two cases that underwent EA between January 2009-December 2019 from 8 referral hospitals including both private practice and academic institutions were reviewed. Post-operative complications were classified as either minor or major, surgical evaluations were performed 8 weeks post operatively, and a follow-up questionnaire was sent to owners. Of the total 22 cases that met inclusion criteria, a total of 19/22 cases had complications, 12 major and 7 minor. Complications reported in 8/9, 7/9, and 4/4, for the DCP, LCP, and ESF fixation groups, respectively. Mild to moderate mechanical lameness was identified at surgical evaluation in 16/22 cases. Complete radiographic bone healing was achieved after 9 weeks in 19/22 cases. Long term owner follow up was available in 14/22 cases. Owners reported a good to normal quality of life in 13/14 cases and poor in one case. The majority of owners (11/14) reported good to excellent satisfaction with the outcome irrespective of persistent lameness. This study demonstrates that successful EA can be achieved using a variety of fixation methods, but persistent lameness is expected and complication rate is high.
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Affiliation(s)
- Elaine V. Dinwiddie
- Small Animal Surgery Department, Veterinary Specialty and Emergency Center, Levittown, PA, United States of America
| | - Aaron Rendahl
- Statistics and Informatics Department, College of Veterinary Medicine at the University of Minnesota, St. Paul, MN, United States of America
| | - Stan Veytsman
- Small Animal Surgery Department, College of Veterinary Medicine at the University of Minnesota, St. Paul, MN, United States of America
| | - Guillaume Ragetly
- Small Animal Surgery Department, Centre Hospitalier Veterinaire Fregis, Arcueil, France
| | - Albert C. Lynch
- Small Animal Surgery Department, Veterinary Specialty and Emergency Center, Levittown, PA, United States of America
| | - Brianna Miniter
- Small Animal Surgery Department, BluePearl Pet Hospital, Clearwater, FL, United States of America
| | - Ron Ben-Amotz
- Small Animal Orthopedics Department, Koret School of Veterinary Medicine at The Hebrew University of Jerusalem, Rehovot, Israel
- * E-mail:
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Sartini I, Giorgi M. Grapiprant: A snapshot of the current knowledge. J Vet Pharmacol Ther 2021; 44:679-688. [PMID: 34057218 PMCID: PMC8518515 DOI: 10.1111/jvp.12983] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/19/2021] [Accepted: 05/11/2021] [Indexed: 12/30/2022]
Abstract
Grapiprant is the pioneer member of the novel piprant class, a potent and specific antagonist of the prostaglandin E2 receptor 4. It has been approved in veterinary medicine for the control of pain and inflammation associated with osteoarthritis in dogs at the dose regimen of 2 mg/kg once a day by the FDA and EMA (for pain only) in 2016 and 2018, respectively. The aim of this narrative review was to report the analytical methods, pharmacokinetics, pharmacodynamics and safety of grapiprant in several animal species using the best available published scientific evidence. In conclusion, most of the analytical methods proposed for grapiprant detection are simple, reliable, sensitive and validated. The pharmacokinetics show discrepancies between animal species. The therapeutic efficacy seems more suited to chronic rather than acute pain.
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Affiliation(s)
- Irene Sartini
- Department of Veterinary Medicine, University of Sassari, Sassari, Italy
| | - Mario Giorgi
- Department of Veterinary Sciences, University of Pisa, Pisa, Italy.,PhD School, Department of Veterinary Medicine, University of Sassari, Sassari, Italy
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Isaksen KE, Linney L, Williamson H, Norman EJ, Cave NJ, Cogger N. TeamMate: A Longitudinal Study of New Zealand Working Farm Dogs. III. Factors Affecting the Risk of Dogs Being Lost from the Workforce. Animals (Basel) 2021; 11:ani11061602. [PMID: 34072311 PMCID: PMC8226994 DOI: 10.3390/ani11061602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 05/27/2021] [Indexed: 11/16/2022] Open
Abstract
Working farm dogs are essential to many livestock farmers. Little is known about factors that influence dogs' risk of being lost from work. This paper explores risk factors for farm dogs being lost through death, euthanasia and retirement. All enrolled dogs were working and a minimum of 18 months old. Five data collection rounds were performed over four years. Data about dogs were collected from owners and dogs were given physical examinations by veterinarians. Dogs that were lost from work were counted and owner-reported reasons for loss were recorded. Multivariable logistic regression modelling was used to investigate risk factors for loss. Of 589 dogs, 81 were lost from work. Of these, 59 dogs died or were euthanized and 22 were retired. Farm dogs tended to reach advanced ages, with 38% being 10 years or older when last examined. Acute injury or illness was the most commonly owner-reported reason for loss. Age group (p < 0.0001) and lameness (p = 0.04, OR = 1.8) significantly affected dogs' risk of being lost. These results expand our knowledge about factors that affect health, welfare and work in farm dogs. Further investigation into reasons for lameness may help improve health and welfare in working farm dogs.
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Affiliation(s)
- Katja E. Isaksen
- School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand; (N.J.C.); (N.C.)
- Correspondence:
| | - Lori Linney
- Vetlife, Timaru 7910, New Zealand; (L.L.); (H.W.)
| | | | | | - Nick J. Cave
- School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand; (N.J.C.); (N.C.)
| | - Naomi Cogger
- School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand; (N.J.C.); (N.C.)
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Glucosamine and Chondroitin Sulfate: Is There Any Scientific Evidence for Their Effectiveness as Disease-Modifying Drugs in Knee Osteoarthritis Preclinical Studies?-A Systematic Review from 2000 to 2021. Animals (Basel) 2021; 11:ani11061608. [PMID: 34072407 PMCID: PMC8228516 DOI: 10.3390/ani11061608] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/19/2021] [Accepted: 05/27/2021] [Indexed: 12/19/2022] Open
Abstract
Simple Summary Osteoarthritis is the most common progressive joint disease diagnosed in companion animals and its management continues to be a significant challenge. Nutraceuticals have been widely investigated over the years in the treatment of osteoarthritis and among them, glucosamine and chondroitin sulfate treatments are probably the most common therapies used in veterinary management. However, heterogeneous results were obtained among animal studies and the evidence of their efficacy is still controversial. Animal models have a crucial role in studying the histological changes and evaluating the therapy efficacy of different drugs. Consequently, we consider it may be of interest to evaluate the effectiveness of the most representative nutraceuticals in experimental animal studies of osteoarthritis. In this systematic review, we found a large inconsistency among the experimental protocols, but a positive cartilage response and biochemical modulation were observed in half of the evaluated articles, mainly associated with pre-emptive administrations and with some therapies’ combinations. Even though some of these results were promising, additional data are needed to draw solid conclusions, and further studies evaluating their efficacy in the long term and focusing on other synovial components may be needed to clarify their function. Abstract Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.
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Brondeel C, Pauwelyn G, de Bakker E, Saunders J, Samoy Y, Spaas JH. Review: Mesenchymal Stem Cell Therapy in Canine Osteoarthritis Research: "Experientia Docet" (Experience Will Teach Us). Front Vet Sci 2021; 8:668881. [PMID: 34095280 PMCID: PMC8169969 DOI: 10.3389/fvets.2021.668881] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 03/29/2021] [Indexed: 12/11/2022] Open
Abstract
Osteoarthritis (OA) is currently an incurable and progressive condition in dogs causing chronic joint pain and possibly increasing disability. Due to the poor healing capacity of cartilage lesions that occur with OA, development of effective therapeutics is difficult. For this reason, current OA therapy is mostly limited to the management of pain and inflammation, but not directed ad disease modification. In the search for a safe and effective OA treatment, mesenchymal stem cells (MSCs) have been of great interest since these cells might be able to restore cartilage defects. The designs of OA studies on MSC usage, however, are not always consistent and complete, which limits a clear evaluation of MSC efficacy. The general study results show a tendency to improve lameness, joint pain and range of motion in dogs suffering from naturally-occurring OA. Assessment of the cartilage surface demonstrated the ability of MSCs to promote cartilage-like tissue formation in artificially created cartilage defects. Immunomodulatory capacities of MSCs also seem to play an important role in reducing pain and inflammation in dogs. It should be mentioned, however, that in the current studies in literature there are specific design limitations and further research is warranted to confirm these findings.
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Affiliation(s)
- Carlien Brondeel
- Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Glenn Pauwelyn
- Global Stem Cell Technology NV, Part of Boehringer-Ingelheim, Evergem, Belgium
| | - Evelien de Bakker
- Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Jimmy Saunders
- Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Yves Samoy
- Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Jan H Spaas
- Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.,Global Stem Cell Technology NV, Part of Boehringer-Ingelheim, Evergem, Belgium
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Magalhães TR, Lourenço AL, Gregório H, Queiroga FL. Therapeutic Effect of EPA/DHA Supplementation in Neoplastic and Non-neoplastic Companion Animal Diseases: A Systematic Review. In Vivo 2021; 35:1419-1436. [PMID: 33910819 DOI: 10.21873/invivo.12394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/24/2021] [Accepted: 03/26/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM The aim of this study is to identify and describe randomized controlled studies evaluating the therapeutic effect of EPA and DHA supplementation in companion animal diseases. MATERIALS AND METHODS A systematic search was conducted in PubMed database and the information collected was summarized and evaluated according to the risk of bias, using the revised Cochrane tool (RoB2). RESULTS Twenty-three studies were eligible for inclusion: twenty performed in dogs and three in cats. A therapeutic benefit was found in canine allergic dermatitis, haircoat disorder, keratoconjunctivitis sicca, valvular disease, and canine and feline osteoarthritis. Dogs diagnosed with chronic heart failure and lymphoma and cats with allergic dermatitis also seem to benefit from supplementation with omega-3 fatty acids, but studies with improved methodological quality are needed to strengthen this evidence. CONCLUSION EPA and DHA supplementation has proven benefits in the adjuvant treatment of various neoplastic and non-neoplastic diseases in dogs and cats.
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Affiliation(s)
| | - Ana Luísa Lourenço
- Department of Animal Science, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.,Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes e Alto Douro, Vila Real, Portugal
| | - Hugo Gregório
- AniCura Centro Hospitalar Veterinário, Porto, Portugal
| | - Felisbina Luísa Queiroga
- Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal; .,Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.,Center for the Study of Animal Sciences, CECA-ICETA, University of Porto, Porto, Portugal
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Koprivec S, Novak M, Bernik S, Voga M, Mohorič L, Majdič G. Treatment of cranial cruciate ligament injuries in dogs using a combination of tibial tuberosity advancement procedure and autologous mesenchymal stem cells/multipotent mesenchymal stromal cells - A pilot study. Acta Vet Hung 2021; 68:405-412. [PMID: 33656452 DOI: 10.1556/004.2020.00063] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 12/21/2020] [Indexed: 12/18/2022]
Abstract
In the present pilot study, we evaluated different supplemental therapies using autologous multipotent mesenchymal stromal cells (MMSCs) for the treatment of cranial cruciate ligament defects in dogs. We used tibial tuberosity advancement (TTA) and augmented it by supportive therapy with MMSCs in three patient groups. In the first patient group, the dogs were injected with MMSCs directly into the treated stifle one month after surgery. In the second group, MMSCs were delivered in a silk fibroin scaffold which was placed in the osteotomy gap during surgery. In the third group, MMSCs were first mixed with bone tissue and blood from the patient and delivered into the osteotomy gap during surgery. In the control group, patients underwent the TTA procedure but did not receive MMSC treatment. In the group of patients who received cells in the silk fibroin scaffold during surgery, the osteotomy gap did not heal, presumably due to the low absorption of silk fibroin. Patients who received MMSCs mixed with bone tissue and blood during surgery into the osteotomy gap recovered clinically faster and had better healing of the osteotomy gap than dogs from the other two treated groups and from the control group, as assessed by clinical examination and quantification of radiographs. In conclusion, dogs that received stem cells directly into the osteotomy gap (Group 3) recovered faster compared to dogs from Groups 1 (MMSCs injected into the joint one month after surgery), 2 (cells implanted into the osteotomy gap in a silk fibroin scaffold), and the control group that did not receive additional MMSCs treatment.
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Affiliation(s)
| | | | | | - Metka Voga
- 2Institute for Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia
| | - Luka Mohorič
- 3Animacel Biotechnology Ltd., Ljubljana, Slovenia
| | - Gregor Majdič
- 2Institute for Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia
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Zhang W, Qiu Q, Sun B, Xu W. A four-genes based diagnostic signature for osteoarthritis. Rheumatol Int 2021; 41:1815-1823. [PMID: 33555399 DOI: 10.1007/s00296-021-04795-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 01/18/2021] [Indexed: 01/12/2023]
Abstract
Osteoarthritis (OA) is a primary leading cause of pain and disability. However, some cases are diagnosed at the later stage which delayed the timely treatment. This study aims to identify effective diagnostic signature for OA. The mRNA profile GSE48566 including 106 blood samples of OA patients and 33 blood samples of healthy individuals was downloaded from Gene Expression Omnibus (GEO) database. The potential OA-related genes were screened by weighted gene co-expression network analysis (WGCNA). Gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to reveal the functions or pathways of OA-related genes using the clusterProfiler function package of R software. Key genes significantly involved in OA progression were further screened by protein-protein interaction (PPI) network. The logistic regression model and the random forest model were conducted by bringing into optimal genes selected by stepwise regression analysis, and fivefold cross validation method was used to determine their reliability. A total of 146 genes, existed in three modules and might be associated with the occurrence of OA, were screened. 15 genes were screened from the PPI network and four genes, including CCR6, CLEC7A, IL18 and SRSF2, were further optimized. Finally, a logistic regression model and a random forest model were conducted by bringing into four optimal genes, and could reliably separate OA patients from healthy subjects. Our study established two effective diagnostic models based on CCR6, CLEC7A, IL18 and SRSF2, which could reliably separate OA patients from healthy subjects.
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Affiliation(s)
- Wenpeng Zhang
- Department of Orthopaedics, Zibo Central Hospital, Zibo, 255036, Shandong, China
| | - Qichang Qiu
- Department of Orthopaedics, People Hospital of Huantai County, Huantai Avenue 2198, Huantai County, Zibo, 255000, Shandong, China
| | - Bo Sun
- Department of Orthopaedics, People Hospital of Huantai County, Huantai Avenue 2198, Huantai County, Zibo, 255000, Shandong, China
| | - Weimin Xu
- Department of Orthopaedics, People Hospital of Huantai County, Huantai Avenue 2198, Huantai County, Zibo, 255000, Shandong, China.
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50
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Schnedeker AH, Cole LK, Diaz SF, Lorch G, Rajala-Shultz PJ, Jennings RN, Hostnik ET, Daniels JB. Is low-level laser therapy useful as an adjunctive treatment for canine acral lick dermatitis? A randomized, double-blinded, sham-controlled study. Vet Dermatol 2021; 32:148-e35. [PMID: 33471429 DOI: 10.1111/vde.12921] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 05/07/2020] [Accepted: 06/13/2020] [Indexed: 12/01/2022]
Abstract
BACKGROUND Conventional therapy for canine acral lick dermatitis (ALD) consists of systemic antibiotics and anti-anxiety medications. Low-level laser therapy (LLLT) is a noninvasive therapy used to treat inflammatory and painful conditions. HYPOTHESIS/OBJECTIVES The primary objective was to determine whether LLLT with conventional therapy would be beneficial as an adjunct treatment for ALD. We hypothesized that LLLT and conventional therapy combined would result in a greater reduction in licking Visual Analog Score (LVAS) compared to conventional therapy alone. Secondary objectives were to assess change in lesion/ulcer size, thickness and hair growth. ANIMALS Thirteen dogs with a skin lesion consistent with ALD. METHODS AND MATERIALS Dogs were randomly assigned to two groups. All dogs received systemic antibiotics and trazodone. The treatment group (TG) received LLLT by laser (130 mW, 2 min) with blue and red light-emitting diodes (LEDs), while the control group (CG) had sham therapy (laser/LEDs off). Treatments were administered three times weekly for two weeks, then twice weekly for two weeks for a total of 10 visits. Descriptive statistics were performed (mean, median); primary and secondary objectives were assessed with nonparametric ANOVA (Kruskal-Wallis test), with significance set at P < 0.05. RESULTS Thirteen dogs (six CG, seven TG) were enrolled. There were no significant differences in median LVAS, lesion/ulcer size or thickness of the ALD lesion between TG and CG. There was a significantly greater increase (24%) in hair growth in TG (P = 0.0081) compared to CG. CONCLUSIONS AND CLINICAL RELEVANCE Treatment of ALD requires multimodal therapy. Although combining LLLT with conventional therapy did not result in a significantly greater reduction in LVAS, there was a significant increase in hair growth compared to conventional therapy alone.
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Affiliation(s)
- Amy H Schnedeker
- VCA SouthPaws Veterinary Specialists & Emergency, 8500 Arlington Blvd, Fairfax, VA, 22031, USA
| | - Lynette K Cole
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp St., Columbus, OH, 43210, USA
| | - Sandra F Diaz
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp St., Columbus, OH, 43210, USA
| | - Gwendolen Lorch
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp St., Columbus, OH, 43210, USA
| | - Päivi J Rajala-Shultz
- Department of Production Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Paroninkuja 20, Saarentaus, 04920, Finland
| | - Ryan N Jennings
- Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA
| | - Eric T Hostnik
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp St., Columbus, OH, 43210, USA
| | - Joshua B Daniels
- Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Colorado State University, 300 West Drake, Road, Fort Collins, CO, 80523, USA
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