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Wang S, Sha P, Zhao X, Tao Z, Liu S. Peritendinous adhesion: Therapeutic targets and progress of drug therapy. Comput Struct Biotechnol J 2024; 23:251-263. [PMID: 38173878 PMCID: PMC10762322 DOI: 10.1016/j.csbj.2023.11.059] [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: 05/15/2023] [Revised: 11/28/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024] Open
Abstract
Peritendinous adhesion (PA) is one of the most common complications following hand surgery and characterized with abnormal hyperplasia of connective tissue and excessive deposition of extracellular matrix. Subsequently, various clinical symptoms such as chronic pain, limb dyskinesia and even joint stiffness occur and patients are always involved in the vicious cycle of "adhesion - release - re-adhesion", which seriously compromise the quality of life. Until present, the underlying mechanism remains controversial and lack of specific treatment, with symptomatic treatment being the only option to relieve symptoms, but not contributing no more to the fundamentally rehabilitation of basic structure and function. Recently, novel strategies have been proposed to inhibit the formation of adhesion tissues including implantation of anti-adhesion barriers, anti-inflammation, restraint of myofibroblast transformation and regulation of collagen overproduction. Furthermore, gene therapy has also been considered as a promising anti-adhesion treatment. In this review, we provide an overview of anti-adhesion targets and relevant drugs to summarize the potential pharmacological roles and present subsequent challenges and prospects of anti-adhesion drugs.
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Affiliation(s)
| | | | | | - Zaijin Tao
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Hanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Shen Liu
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Hanghai Jiao Tong University School of Medicine, Shanghai 200233, China
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Najafi Z, Rahmanian-Devin P, Baradaran Rahimi V, Nokhodchi A, Askari VR. Challenges and opportunities of medicines for treating tendon inflammation and fibrosis: A comprehensive and mechanistic review. Fundam Clin Pharmacol 2024; 38:802-841. [PMID: 38468183 DOI: 10.1111/fcp.12999] [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: 09/16/2023] [Revised: 01/20/2024] [Accepted: 02/19/2024] [Indexed: 03/13/2024]
Abstract
BACKGROUND Tendinopathy refers to conditions characterized by collagen degeneration within tendon tissue, accompanied by the proliferation of capillaries and arteries, resulting in reduced mechanical function, pain, and swelling. While inflammation in tendinopathy can play a role in preventing infection, uncontrolled inflammation can hinder tissue regeneration and lead to fibrosis and impaired movement. OBJECTIVES The inability to regulate inflammation poses a significant limitation in tendinopathy treatment. Therefore, an ideal treatment strategy should involve modulation of the inflammatory process while promoting tissue regeneration. METHODS The current review article was prepared by searching PubMed, Scopus, Web of Science, and Google Scholar databases. Several treatment approaches based on biomaterials have been developed. RESULTS This review examines various treatment methods utilizing small molecules, biological compounds, herbal medicine-inspired approaches, immunotherapy, gene therapy, cell-based therapy, tissue engineering, nanotechnology, and phototherapy. CONCLUSION These treatments work through mechanisms of action involving signaling pathways such as transforming growth factor-beta (TGF-β), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), all of which contribute to the repair of injured tendons.
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Affiliation(s)
- Zohreh Najafi
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Pouria Rahmanian-Devin
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vafa Baradaran Rahimi
- Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Nokhodchi
- Lupin Pharmaceutical Research Center, 4006 NW 124th Ave., Coral Springs, Florida, Florida, 33065, USA
- Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Brighton, BN1 9QJ, UK
| | - Vahid Reza Askari
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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3
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Chung SW, Chung SH, Kim DH, Lee HJ, Park EJ, Shim BJ, Cho CH, Yoon JP. Biomechanical and histological evaluation of aspirin in rotator cuff tear rat model. J Orthop Surg (Hong Kong) 2024; 32:10225536241265827. [PMID: 39089684 DOI: 10.1177/10225536241265827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/04/2024] Open
Abstract
Background: Aspirin is a representative non-steroidal anti-inflammatory drug (NSAIDs) and has been commonly used for the treatment of tendinopathy in clinical practice. In this study, we aimed to evaluate the biomechanical and histological healing effects of aspirin on the healing of the tendon-to-bone interface after rotator cuff tear repair. Methods: A total of 20 male Sprague-Dawley rats were randomly divided into two groups of 10 rats each. Group-C performed repaironly, and group-aspirin treated with aspirin after tendon repair. Group-aspirin rat were intraperitoneally injected with aspirin at 10 mg/kg every 24 h for 7 days. Eight weeks after surgery, the left shoulder of each rat was used for histological analysis and the right shoulder for biomechanical analysis. Results: In the biomechanical analysis, there was no significant difference in load-to-failure (group-C: 0.61 ± 0.32 N, group-aspirin: 0.74 ± 0.91 N; p = .697) and ultimate stress (group-C: 0.05 ± 0.01 MPa, group-aspirin: 0.29 ± 0.43 MPa; p = .095). For the elongation (group-C: 222.62 ± 57.98%, group-aspirin: 194.75 ± 75.16%; p = .028), group-aspirin confirmed a lower elongation level than group-C. In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 1.60 ± 0.52, group-aspirin: 2.60 ± 0.52, p = .001) and vascularity (group-C: 1.00 ± 0.47, group-aspirin: 2.20 ± 0.63, p = .001) between the groups. Conclusions: Aspirin injection after rotator cuff tear repair may enhance the healing effect during the early remodeling phase of tendon healing.
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Affiliation(s)
- Seok Won Chung
- Department of Orthopaedic Surgery, School of Medicine, Konkuk University Medical Center, Seoul, Republic of Korea
| | - Seung Ho Chung
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Dong-Hyun Kim
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Hyun Joo Lee
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Eugene J Park
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Bum-Jin Shim
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Chul-Hyun Cho
- Department of Orthopedic Surgery, Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Jong Pil Yoon
- Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
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Shi G, Koichi N, Wan R, Wang Y, Reisdorf R, Wilson A, Huang TC, Amadio PC, Meves A, Zhao C, Moran SL. Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon. J Orthop Translat 2024; 45:75-87. [PMID: 38511123 PMCID: PMC10950576 DOI: 10.1016/j.jot.2023.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 10/14/2023] [Accepted: 10/26/2023] [Indexed: 03/22/2024] Open
Abstract
Background Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. Methods In this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. Results Pentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. Conclusions We tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this article This study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.
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Affiliation(s)
- Guidong Shi
- Department of Orthopaedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Nakagawa Koichi
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Rou Wan
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Yicun Wang
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Ramona Reisdorf
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Abigayle Wilson
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Tony C.T. Huang
- Division of Plastic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Peter C. Amadio
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Chunfeng Zhao
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Steven L. Moran
- Division of Plastic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
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5
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Chen SY, Jou IM, Ko PY, Hsu KL, Su WR, Kuo LC, Lee PY, Wu CL, Wu PT. Amelioration of experimental tendinopathy by lentiviral CD44 gene therapy targeting senescence-associated secretory phenotypes. Mol Ther Methods Clin Dev 2022; 26:157-168. [PMID: 35846572 PMCID: PMC9254001 DOI: 10.1016/j.omtm.2022.06.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 06/07/2022] [Indexed: 01/14/2023]
Abstract
CD44 exerts anti-senescence effects in many disease models. We examined senescence in tendinopathy and the effect of CD44 on senescence-associated secretory phenotypes (SASPs). Senescent markers were determined in human tendinopathic long head of bicep (LHB) and normal hamstring tendons. CD44 gene transfer in rat tendinopathic tenocytes stimulated with interleukin (IL)-1β and a rat Achilles tendinopathy model were performed using lentiviral vectors. Expression levels of p53, p21, and p16 and senescence-associated β-galactosidase (SA-β-gal) activity were positively correlated with the severity of human tendinopathy and were higher in rat and human tendinopathic tenocytes than in normal controls. CD44 overexpressed tenocyte transfectants exhibited reduced levels of IL-6, matrix metalloproteinases (MMPs), cyclooxygenase (COX)-2, p53, p21, p16, SA-β-gal, and phospho-nuclear factor (NF)-κB, whereas their collagen type I alpha 1 (COL1A1) and tenomodulin (tnmd) levels were increased when compared with control transfectants under IL-1β-stimulated conditions. In the animal model, CD44 overexpression lowered the ultrasound and histology scores and expression levels of the senescent and SASP markers COX-2 and phospho-NF-κB. Bromodeoxyuridine (BrdU)- and tnmd-positive cell numbers were increased in the LVCD44-transduced tendinopathic tendons. Senescence is positively correlated with tendinopathic severity, and CD44 overexpression may protect the tendinopathic tendons from SASPs via anti-inflammation and maintenance of extracellular matrix homeostasis.
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Affiliation(s)
- Shih-Yao Chen
- Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan
| | - I-Ming Jou
- Department of Orthopaedics, E-Da Hospital, Kaohsiung 82445, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
| | - Po-Yen Ko
- Department of Orthopaedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.,Department of Biomedical Engineering, National Cheng Kung University, Tainan 70101, Taiwan
| | - Kai-Lan Hsu
- Department of Orthopaedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.,Department of Biomedical Engineering, National Cheng Kung University, Tainan 70101, Taiwan
| | - Wei-Ren Su
- Department of Orthopaedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.,Department of Orthopaedics, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
| | - Li-Chieh Kuo
- Department of Occupational Therapy, National Cheng Kung University, Tainan 70101, Taiwan.,Medical Device Innovation Center, National Cheng Kung University, Tainan 70101, Taiwan
| | - Pei-Yuan Lee
- Department of Orthopaedic Surgery, Show Chwan Memorial Hospital, Changhua 50544, Taiwan.,College of Nursing and Health Sciences, Da-Yeh University, Changhua 51500, Taiwan
| | - Chao-Liang Wu
- Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.,Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan
| | - Po-Ting Wu
- Department of Orthopaedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.,Department of Biomedical Engineering, National Cheng Kung University, Tainan 70101, Taiwan.,Department of Orthopaedics, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.,Medical Device Innovation Center, National Cheng Kung University, Tainan 70101, Taiwan.,Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
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Cai Z, Zhang Y, Liu S, Liu X. Celecoxib, Beyond Anti-inflammation, Alleviates Tendon-Derived Stem Cell Senescence in Degenerative Rotator Cuff Tendinopathy. Am J Sports Med 2022; 50:2488-2496. [PMID: 35666137 DOI: 10.1177/03635465221098133] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Degenerative rotator cuff tendinopathy (RCT) is associated with the senescence of tendon-derived stem cells (TDSCs). Nonsteroidal anti-inflammatory drugs have been demonstrated to alleviate age-associated inflammation (inflamm-aging)-induced cellular senescence of skeletal stem/progenitor cells. However, whether they can alleviate degenerative RCT through reducing inflamm-aging-related TDSC senescence is still unknown. PURPOSE To assess whether celecoxib can prevent the inflamm-aging-related cellular senescence of TDSCs. STUDY DESIGN Controlled laboratory study. METHODS TDSCs were isolated from degenerative RCT tendons (S-TDSCs) and healthy hamstring tendons (Y-TDSCs), and the cellular senescence of TDSCs was evaluated. Thereafter, the senescent TDSC-conditioned medium (SEN-CM) was collected to culture Y-TDSCs with or without celecoxib. The effects of celecoxib on TDSC senescence were examined by assaying the expression of aging-related markers. Furthermore, the level of the NF-κB pathway was determined by Western blot analysis to explore the underlying mechanism. Its effects on preventing dysfunction of inflamm-aging-induced senescent TDSCs were also determined using multilineage differentiation assay. RESULTS S-TDSCs showed increased senescence-associated β-galactosidase activity and enhanced expression of γ-H2AX, p21CIP1A, p16INK4A, and senescence-associated secretory phenotype factors. SEN-CM accelerated the senescence progress of Y-TDSCs, resulting in an increase in senescence markers. To some extent, celecoxib treatment could prevent the detrimental effects of inflamm-aging on Y-TDSCs. The level of the NF-κB pathway was increased in the SEN-CM group but decreased with the use of celecoxib. Moreover, the reduced senescence of TDSCs resulted in preservation of the TDSC tenogenic potential. CONCLUSION Celecoxib treatment can prevent inflamm-aging-induced TDSC senescence, which holds potential for alleviating the development of degenerative RCT. CLINICAL RELEVANCE In addition to relieving the symptoms of patients with RCT, treatment with celecoxib, a common nonsteroidal anti-inflammatory drug, may defer the development of RCT and prevent rotator cuff tears by delaying TDSC senescence.
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Affiliation(s)
- Zhuochang Cai
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yao Zhang
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Shen Liu
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Xudong Liu
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
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7
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Supokawej A, Korchunjit W, Wongtawan T. The combination of BMP12 and KY02111 enhances tendon differentiation in bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs). J Equine Sci 2022; 33:19-26. [PMID: 35847484 PMCID: PMC9260033 DOI: 10.1294/jes.33.19] [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: 01/27/2022] [Accepted: 05/10/2022] [Indexed: 11/18/2022] Open
Abstract
The Wingless and Int-1 (WNT) and bone morphogenic protein/growth differentiation factor
(BMP/GDF) signalling pathways contribute significantly to the development of the
musculoskeletal system. The mechanism by which they contribute is as follows: BMP/GDF
signalling usually promotes tendon differentiation, whereas WNT signalling inhibits it. We
hypothesised that inhibiting WNT and subsequently stimulating BMP signalling may enhance
the tenogenic differentiation of stem cells. The objective of this study was to determine
whether a combination of WNT inhibitor (KY02111) and BMP12/GDF7 protein could enhance the
differentiation of bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs) into
tenocytes. Cells were cultured in five treatments: control, BMP12, and three different
combinations of BMP12 and KY02111. The results indicated that a 1-day treatment with
KY02111 followed by a 13-day treatment with BMP12 resulted in the highest tenogenic
differentiation score in this experiment. The effect of KY02111 is dependent on the
incubation time, with 1 day being better than 3 or 5 days. This combination increased
tenogenic gene marker expression, including SCX, TNMD, DCN, and TNC, as well as COL1
protein expression. In conclusion, we propose that a combination of BMP12 and KY02111 can
enhance the in vitro tenogenic differentiation of BM-eMSCs more than BMP12 alone. The
findings of this study might be useful for improving tendon differentiation protocols for
stem cell transplantation and application to tendon regeneration.
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Affiliation(s)
- Aungkura Supokawej
- Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Wasamon Korchunjit
- Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand.,Laboratory of Cellular Biomedicine, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Tuempong Wongtawan
- Akkhararatchakumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand.,Centre for One Health, Walailak University, Nakhon Si Thammarat 80160, Thailand.,Laboratory of Cellular Biomedicine, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand
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8
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Sakaguchi T, Ohkawara B, Kishimoto Y, Miyamoto K, Ishizuka S, Hiraiwa H, Ishiguro N, Imagama S, Ohno K. Promethazine Downregulates Wnt/β-Catenin Signaling and Increases the Biomechanical Forces of the Injured Achilles Tendon in the Early Stage of Healing. Am J Sports Med 2022; 50:1317-1327. [PMID: 35234523 DOI: 10.1177/03635465221077116] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Wnt/β-catenin signaling suppresses the differentiation of cultured tenocytes, but its roles in tendon repair remain mostly elusive. No chemical compounds are currently available to treat tendon injury. HYPOTHESIS We hypothesized that the inhibition of Wnt/β-catenin signaling would accelerate tendon healing. STUDY DESIGN Controlled laboratory study. METHODS Tendon-derived cells (TDCs) were isolated from rat Achilles tendons. The right Achilles tendon was injured via a dermal punch, while the left tendon was sham operated. A Wnt/β-catenin inhibitor, IWR-1, and an antihistamine agent, promethazine (PH), were locally and intramuscularly injected, respectively, for 2 weeks after surgery. The healing tendons were histologically and biomechanically evaluated. RESULTS The amount of β-catenin protein was increased in the injured tendons from postoperative weeks 0.5 to 2. Inhibition of Wnt/β-catenin signaling by IWR-1 in healing tendons improved the histological abnormalities and decreased β-catenin, but it compromised the biomechanical properties. As we previously reported that antihistamine agents suppressed Wnt/β-catenin signaling in human chondrosarcoma cells, we examined the effects of antihistamines on TDCs. We found that a first-generation antihistamine agent, PH, increased the expression of the tendon marker genes Mkx and Tnmd in TDCs. Intramuscular injection of PH did not improve histological abnormalities, but it decreased β-catenin in healing tendons and increased the peak force and stiffness of the healing tendons on postoperative week 2. On postoperative week 8, however, the biomechanical properties of vehicle-treated tendons became similar to those of PH-treated tendons. CONCLUSION IWR-1 and PH suppressed Wnt/β-catenin signaling and improved the histological abnormalities of healing tendons. IWR-1, however, compromised the biomechanical properties of healing tendons, whereas PH improved them. CLINICAL RELEVANCE PH is a candidate repositioned drug that potentially accelerates tendon repair.
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Affiliation(s)
- Takefumi Sakaguchi
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Japan.,Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Bisei Ohkawara
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Yasuzumi Kishimoto
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Japan.,Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Kentaro Miyamoto
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Japan.,Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Shinya Ishizuka
- Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Hideki Hiraiwa
- Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Naoki Ishiguro
- Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Shiro Imagama
- Department of Orthopaedic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Kinji Ohno
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Japan
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Zafarmand SS, Karimi-Haghighi S, Salehi MS, Hooshmandi E, Owjfard M, Bayat M, Karimlou S, Pandamooz S, Dianatpour M, Borhani-Haghighi A. Aspirin impacts on stem cells: Implications for therapeutic targets. Tissue Cell 2021; 74:101707. [PMID: 34883315 DOI: 10.1016/j.tice.2021.101707] [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: 09/06/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 11/27/2022]
Abstract
Despite the regenerative potential of stem cell therapy in pre-clinical investigations, clinical translation of cell-based therapy has not been completely clarified. In recent years, the importance of lifestyle, patient comorbidities, and prescribed medication has attracted more attention in the efficacy of cell therapy. As a nonsteroidal anti-inflammatory drug, aspirin is one of the most prevalent prescribed medications in the clinic for various disorders. Hence, aspirin treatment might affect the efficacy of stem cell therapy. In this regard, the current review focused on the impacts of aspirin on the viability, proliferation, differentiation, and immunomodulatory properties of stem cells in vitro as well as in experimental animal models.
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Affiliation(s)
| | | | - Mohammad Saied Salehi
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Etrat Hooshmandi
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Owjfard
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahnaz Bayat
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sedigheh Karimlou
- Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sareh Pandamooz
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Dianatpour
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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10
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Acetylsalicylic Acid Enhanced Neurotrophic Profile of Epidermal Neural Crest Stem Cells: A Possible Approach for the Combination Therapy. PHYSIOLOGY AND PHARMACOLOGY 2021. [DOI: 10.52547/phypha.26.2.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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11
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Wei B, Lu J. Characterization of Tendon-Derived Stem Cells and Rescue Tendon Injury. Stem Cell Rev Rep 2021; 17:1534-1551. [PMID: 33651334 DOI: 10.1007/s12015-021-10143-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2021] [Indexed: 12/12/2022]
Abstract
The natural healing ability of tendon is limited, and it cannot restore the native structure and function of tendon injuries. Tendon-derived stem cells (TDSCs) are a new type of pluripotent stem cells with multi-directional differentiation potential and are expected to become a promising cell-seed for the treatment of tendon injuries in the future. In this review, we outline the latest advances in the culture and identification of TDSCs. In addition, the influencing factors on the differentiation of TDSCs are discussed. Moreover, we aim to discuss recent studies to enhance TDSCs treatment of injured tendons. Finally, we identify the limitations of the current understanding of TDSCs biology, the main challenges of using their use, and potential therapeutic strategies to inform cell-based tendon repair.
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Affiliation(s)
- Bing Wei
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Jun Lu
- Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
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12
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Pan Y, Cheng A, Zhang X, Wang M, Chen S, Zhu D, Liu M, Zhao X, Yang Q, Wu Y, Huang J, Zhang S, Mao S, Ou X, Gao Q, Yu Y, Liu Y, Zhang L, Yin Z, Jing B, Tian B, Pan L, Rehman MU, Chen X, Jia R. Transcriptome analysis of duck embryo fibroblasts for the dynamic response to duck tembusu virus infection and dual regulation of apoptosis genes. Aging (Albany NY) 2020; 12:17503-17527. [PMID: 32897243 PMCID: PMC7521532 DOI: 10.18632/aging.103759] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 07/02/2020] [Indexed: 01/24/2023]
Abstract
Duck Tembusu virus (DTMUV) is an emerging pathogenic flavivirus that has caused enormous economic losses in Southeast Asia. However, the pathogenic mechanism and host's responses after DTMUV infection remain poorly understood. During this study, total mRNA sequencing (RNA-Seq) analysis was used to detect the global gene expression in DEFs at various time points after DTMUV infection. We identified 326 genes altered significantly at all time points, and these genes were dynamically enriched in multifarious biological processes, including apoptosis, innate immune response, DNA replication, cell cycle arrest and DNA repair. Next, the results showed that apoptosis was induced and the proportion of apoptosis increased with time, and pro-apoptotic molecules caspases were activated. The RNA-seq data analysis further revealed that most pro-apoptosis and anti-apoptosis genes were early continually responsive, and the genes involved in both intrinsic and extrinsic apoptotic pathways were initiated. Further, the considerably enriched immune-relevant pathways were involved in apoptosis process, and protein-protein interactions (PPIs) analysis showed that IL6, STAT1, TNFAIP3, CFLAR and PTGS2 may be key regulators of DEFs apoptosis. In conclusion, this study not only contributes to understanding the underlying mechanism of DEFs infection with DTMUV, but also provides new insights into targets screening for antiviral therapy.
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Affiliation(s)
- Yuhong Pan
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Anchun Cheng
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Xingcui Zhang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Mingshu Wang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Shun Chen
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Dekang Zhu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Mafeng Liu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Xinxin Zhao
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Qiao Yang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Ying Wu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Juan Huang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Shaqiu Zhang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Sai Mao
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Xumin Ou
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Qun Gao
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Yanling Yu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Yunya Liu
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Ling Zhang
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Zhongqiong Yin
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Bo Jing
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Bin Tian
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Leichang Pan
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Mujeeb Ur Rehman
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Xiaoyue Chen
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
| | - Renyong Jia
- Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
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Chen L, Bao J, Yang Y, Wang Z, Xia M, Tan J, Zhou L, Wu Y, Sun W. Autophagy was involved in tumor necrosis factor-α-inhibited osteogenic differentiation of murine calvarial osteoblasts through Wnt/β-catenin pathway. Tissue Cell 2020; 67:101401. [PMID: 32835949 DOI: 10.1016/j.tice.2020.101401] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 06/25/2020] [Accepted: 06/26/2020] [Indexed: 02/06/2023]
Abstract
Periodontitis is an inflammatory disease with a high incidence characterized by irreversible destruction of alveolar bone. This study aimed to investigate the effect of tumor necrosis factor-α (TNF-α) on osteogenic differentiation and its molecular mechanism. TNF-α inhibited osteogenic differentiation as revealed by the lower accumulation of osteoblastic genes like runt-related transcription factor (Runx2), alkaline phosphatase (ALP), osteoprotegerin (OPG), and osteocalcin (OCN). Moreover, TNF-α down-regulated the expressions of LC3II, ATG7, and beclin 1 (BECN1); suggesting that autophagy was inhibited during the process of osteogenic differentiation. Consistently, Wnt/β-catenin signaling pathway members such as low-density lipoprotein receptor-related protein 5 (LRP5), β-catenin, and phosphorylated-β-catenin (p-β-catenin) were reduced by TNF-α. Furthermore, the inhibitory effect of TNF-α on osteogenic differentiation and the Wnt/β-catenin signaling pathway could be abated by autophagy inducers but exacerbated by autophagy inhibitors. The most intriguing finding of all was that TNF-α inhibited osteoblastic differentiation and the Wnt/β-catenin signaling pathway by down-regulating autophagy, and autophagy positively regulated the Wnt/β-catenin pathway and thus influenced osteoblastic differentiation. Our study provides a theoretical basis for autophagy-inducer therapy for the alveolar bone loss caused by periodontitis.
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Affiliation(s)
- Lili Chen
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Jiaqi Bao
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China; Cancer Institute, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China
| | - Yuting Yang
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Zhongxiu Wang
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Mengjiao Xia
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Jingyi Tan
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Lili Zhou
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Yanmin Wu
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Weilian Sun
- Department of Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
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14
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Li K, Deng Y, Deng G, Chen P, Wang Y, Wu H, Ji Z, Yao Z, Zhang X, Yu B, Zhang K. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells. Stem Cell Res Ther 2020; 11:131. [PMID: 32197645 PMCID: PMC7082977 DOI: 10.1186/s13287-020-01643-5] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 02/27/2020] [Accepted: 03/10/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Hypercholesterolemia increases the risk of tendon pain and tendon rupture. Tendon-derived stem cells (TDSCs) play a vital role in the development of tendinopathy. Our previous research found that high cholesterol inhibits tendon-related gene expression in TDSCs. Whether high cholesterol has other biological effects on TDSCs remains unknown. METHODS TDSCs isolated from female SD rats were exposed to 10 mg/dL cholesterol for 24 h. Then, cell apoptosis was assessed using flow cytometry and fluorescence microscope. RFP-GFP-LC3 adenovirus transfection was used for measuring autophagy. Signaling transduction was measured by immunofluorescence and immunoblotting. In addition, Achilles tendons from ApoE -/- mice fed with a high-fat diet were histologically assessed using HE staining and immunohistochemistry. RESULTS In this work, we verified that 10 mg/dL cholesterol suppressed cell proliferation and migration and induced G0/G1 phase arrest. Additionally, cholesterol induced apoptosis and autophagy simultaneously in TDSCs. Apoptosis induction was related to increased expression of cleaved caspase-3 and BAX and decreased expression of Bcl-xL. The occurrence of autophagic flux and accumulation of LC3-II demonstrated the induction of autophagy by cholesterol. Compared with the effects of cholesterol treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) enhanced apoptosis, while the apoptosis inhibitor Z-VAD-FMK diminished cholesterol-induced autophagy. Moreover, cholesterol triggered reactive oxygen species (ROS) generation and activated the AKT/FOXO1 pathway, while the ROS scavenger NAC blocked cholesterol-induced activation of the AKT/FOXO1 pathway. NAC and the FOXO1 inhibitor AS1842856 rescued the apoptosis and autophagy induced by cholesterol. Finally, high cholesterol elevated the expression of cleaved caspase-3, Bax, LC3-II, and FOXO1 in vivo. CONCLUSION The present study indicated that high cholesterol induced apoptosis and autophagy through ROS-activated AKT/FOXO1 signaling in TDSCs, providing new insights into the mechanism of hypercholesterolemia-induced tendinopathy. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.
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Affiliation(s)
- Kaiqun Li
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China
| | - Ye Deng
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China
| | - Ganming Deng
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.,Baoan District People's Hospital of Shenzhen, Shenzhen, 518100, China
| | - Pengyu Chen
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China
| | - Yutian Wang
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China
| | - Hangtian Wu
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China
| | - Zhiguo Ji
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China
| | - Zilong Yao
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China
| | - Xianrong Zhang
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.,Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Bin Yu
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China. .,Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
| | - Kairui Zhang
- Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
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15
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Wang Y, He G, Wang F, Zhang C, Ge Z, Zheng X, Deng H, Yuan C, Zhou B, Tao X, Zhang J, Tang K. Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling. J Cell Mol Med 2019; 23:7535-7544. [PMID: 31557405 PMCID: PMC6815914 DOI: 10.1111/jcmm.14622] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 07/16/2019] [Accepted: 08/04/2019] [Indexed: 01/25/2023] Open
Abstract
Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non‐steroidal anti‐inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti‐inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin‐treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO‐Ohpic and IGF‐1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down‐regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.
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Affiliation(s)
- Yunjiao Wang
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Gang He
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Feng Wang
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Chenke Zhang
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Zilu Ge
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Xiaolong Zheng
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Honghao Deng
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Chengsong Yuan
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Binghua Zhou
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Xu Tao
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Jiqiang Zhang
- Department of Neurology, Third Military Medical University, Chongqing, China
| | - Kanglai Tang
- Department of Orthopaedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
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16
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Dai GC, Li YJ, Chen MH, Lu PP, Rui YF. Tendon stem/progenitor cell ageing: Modulation and rejuvenation. World J Stem Cells 2019; 11:677-692. [PMID: 31616543 PMCID: PMC6789185 DOI: 10.4252/wjsc.v11.i9.677] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 08/15/2019] [Accepted: 09/04/2019] [Indexed: 02/06/2023] Open
Abstract
Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.
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Affiliation(s)
- Guang-Chun Dai
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ying-Juan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China
| | - Min-Hao Chen
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Pan-Pan Lu
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China.
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17
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Li P, Zhao S, Hu Y. SFRP2 modulates non‑small cell lung cancer A549 cell apoptosis and metastasis by regulating mitochondrial fission via Wnt pathways. Mol Med Rep 2019; 20:1925-1932. [PMID: 31257495 DOI: 10.3892/mmr.2019.10393] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 05/20/2019] [Indexed: 11/05/2022] Open
Abstract
The secreted frizzled‑related protein 2 (SFRP2) has been reported to inhibit non‑small cell lung cancer (NSCLC) cell survival and metastasis; however, the underlying mechanisms are yet to be fully determined. The present study focused on mitochondrial fission and the Wnt signaling pathway. The results demonstrated that SFRP2 was downregulated in the NSCLC cell line A549 compared with in a normal pulmonary epithelial cell line using western blotting, reverse transcription‑quantitative PCR and immunofluorescence. Subsequently, it was demonstrated that SFRP2 overexpression promoted the apoptosis, and inhibited the proliferation and metastasis of A549 cells using MTT assays, TUNEL staining and 5‑ethynyl‑2'‑deoxyuridine labeling. At the molecular level, the overexpression of SFRP2 in A549 cells led to the activation of mitochondrial fission by inhibiting the Wnt signal pathway. Excessive mitochondrial fission induced low ATP generation, impaired mitochondrial respiratory function, induced mitochondrial potential depolarization, and increased mitochondrial permeability transition pore opening, and imbalances in pro‑ and antiapoptotic protein expression. Furthermore, mitochondrial fission was involved in the inhibition of A549 cell proliferation and metastasis. Thus, SFRP2 may inhibit the survival and metastasis of NSCLC cells via the Wnt/mitochondrial fission pathway.
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Affiliation(s)
- Peng Li
- Department of Oncology, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Shu Zhao
- Department of Oncology, Τhe Second Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
| | - Yi Hu
- Department of Oncology, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
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18
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Wang Y, He G, Tang H, Shi Y, Kang X, Lyu J, Zhu M, Zhou M, Yang M, Mu M, Chen W, Zhou B, Zhang J, Tang K. Aspirin inhibits inflammation and scar formation in the injury tendon healing through regulating JNK/STAT-3 signalling pathway. Cell Prolif 2019; 52:e12650. [PMID: 31225686 PMCID: PMC6668964 DOI: 10.1111/cpr.12650] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 05/05/2019] [Accepted: 05/17/2019] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVELY Tendinopathy is a common problem in sports medicine which can lead to severe morbidity. Aspirin, as the classical representative of non-steroidal anti-inflammatory drugs (NSAIDs) for its anti-inflammatory and analgesic actions, has been commonly used in treating tendinopathy. While its treatment effects on injury tendon healing are lacking, illuminating the underlying mechanism may provide scientific basis for clinical treatment. MATERIALS AND METHODS Firstly, we used immunohistochemistry and qRT-PCR to detect changes in CD14, CD206, iNOS, IL-6, IL-10, MMP-3, TIMP-3, Col-1a1, biglycan, Comp, Fibronectin, TGF-β1，ACAN，EGR-1 and FMOD. Next, Western blot was used to measure the protein levels (IL-6, IL-10, TGF-β1, COMP, TIMP-3, STAT-3/P-STAT-3 and JNK/P-JNK) in TSCs. Then, migration and proliferation of TSCs were measured through wound healing test and BrdU staining. Finally, the mechanical properties of injury tendon were detected. RESULTS After aspirin treatment, the inflammation and scar formation in injury tendon were significantly inhibited by aspirin. Still, tendon's ECM was positively balanced. Increasing migration and proliferation ability of TSCs induced by IL-1β were significantly reversed. JNK/STAT-3 signalling pathway participated in the process above. In addition, biomechanical properties of injury tendon were significantly improved. CONCLUSIONS Taken together, the findings suggested that aspirin inhibited inflammation and scar formation via regulation of JNK/STAT-3 signalling and decreased rerupture risk of injury tendon. Aspirin could be an ideal therapeutic strategy in tendon injury healing.
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Affiliation(s)
- Yunjiao Wang
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Gang He
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Hong Tang
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Youxing Shi
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Xia Kang
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Jingtong Lyu
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Min Zhu
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Mei Zhou
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Mingyu Yang
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Miduo Mu
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Wan Chen
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Binghua Zhou
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Jiqiang Zhang
- Department of Neurology, Third Military Medical University, Chongqing, China
| | - Kanglai Tang
- Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China
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Cheng XX, Yang QY, Qi YL, Liu ZZ, Liu D, He S, Yang LH, Xie J. Apoptosis of mesenchymal stem cells is regulated by Rspo1 via the Wnt/β-catenin signaling pathway. Chronic Dis Transl Med 2019; 5:53-63. [PMID: 30993264 PMCID: PMC6450805 DOI: 10.1016/j.cdtm.2019.02.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Indexed: 01/19/2023] Open
Abstract
Objective The aim of this study was to investigate the effect and possible mechanism of action of roof plate-specific spondin1 (Rspo1) in the apoptosis of rat bone marrow mesenchymal stem cells (BMSCs). Methods Osteogenic and adipogenic differentiation of BMSCs was identified by Alizarin Red and Oil Red O staining, respectively. BMSC surface markers (cluster of differentiation 29 [CD29], CD90, and CD45) were detected using flow cytometry. BMSCs were transfected with an adenoviral vector encoding Rspo1 (BMSCs-Rspo1 group). The expression levels of Rspo1 gene and Rspo1 protein in the BMSCs-Rspo1 group and the two control groups (untransfected BMSCs group and BMSCs-green fluorescent protein [GFP] group) were analyzed and compared by quantitative polymerase chain reaction and Western blot. The occurrence of apoptosis in the three groups was detected by flow cytometry and acridine orange-ethidium bromide (AO-EB) double dyeing. The activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the expression levels of the key proteins of the pathway (β-catenin, c-Jun N-terminal kinase [JNK], and phospho-JNK). Results Osteogenic and adipogenic differentiation was confirmed in cultured BMSCs by the positive expression of CD29 and CD90 and the negative expression of CD45. Significantly increased expression levels of Rspo1 protein in the BMSCs-Rspo1 group compared to those in the BMSCs (0.60 ± 0.05 vs. 0.13 ± 0.02; t=95.007, P=0.001) and BMSCs-GFP groups (0.60 ± 0.05 vs. 0.10 ± 0.02; t=104.842, P=0.001) were observed. The apoptotic rate was significantly lower in the BMSCs-Rspo1 group compared with those in the BMSCs group ([24.06 ± 2.37]% vs. [40.87 ± 2.82]%; t = 49.872, P = 0.002) and the BMSCs-GFP group ([24.06 ± 2.37]% vs. [42.34 ± 0.26]%; t = 62.358, P = 0.001). In addition, compared to the BMSCs group, the protein expression levels of β-catenin (2.67 ± 0.19 vs. 1.14 ± 0.14; t = −9.217, P = 0.000) and JNK (1.87 ± 0.17 vs. 0.61 ± 0.07; t = −22.289, P = 0.000) were increased in the BMSCs-Rspo1 group. Compared to the BMSCs-GFP group, the protein expression levels of β-catenin (2.67 ± 0.19 vs. 1.44 ± 0.14; t = −5.692, P = 0.000) and JNK (1.87 ± 0.17 vs. 0.53 ± 0.06; t = −10.589, P = 0.000) were also upregulated in the BMSCs-Rspo1 group. Moreover, the protein expression levels of phospho-JNK were increased in the BMSCs-Rspo1 group compared to those in the BMSCs group (1.89 ± 0.10 vs. 0.63 ± 0.09; t = −8.975, P = 0.001) and the BMSCs-GFP group (1.89 ± 0.10 vs. 0.69 ± 0.08; t = −9.483, P = 0.001). Conclusion The Wnt/β-catenin pathway could play a vital role in the Rspo1-mediated inhibition of apoptosis in BMSCs.
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Affiliation(s)
- Xiao-Xia Cheng
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Qiao-Yan Yang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China.,The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Yong-Li Qi
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China.,Huaihe Hospital of Henan University, Kaifeng, Henan 475000, China
| | - Zhi-Zhen Liu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Dan Liu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Sheng He
- The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Li-Hong Yang
- Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jun Xie
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
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Mohamed WA, Abd-Elhakim YM, Ismail SAA. Involvement of the anti-inflammatory, anti-apoptotic, and anti-secretory activity of bee venom in its therapeutic effects on acetylsalicylic acid-induced gastric ulceration in rats. Toxicology 2019; 419:11-23. [PMID: 30885738 DOI: 10.1016/j.tox.2019.03.003] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 02/21/2019] [Accepted: 03/12/2019] [Indexed: 12/11/2022]
Abstract
Acetylsalicylic acid (ASA) is the most highly consumed pharmaceutical product worldwide. Importantly, gastrointestinal ulceration due to ASA is a major complication. Hence, the present work aimed to examine, for the first time, the healing properties of bee venom (BV) in acute gastric ulceration induced by ASA. Forty adult male Sprague-Dawley rats were divided into four groups that received distilled water only, ASA (500 mg/kg BW) twice daily for 3 days, ASA for 3 days followed by BV (2 mg/kg BW) for 7 days, or ASA for 3 days followed by ranitidine hydrochloride (50 mg/kg BW) for 7 days. Haematological analysis, haemostatic evaluation, and inflammatory marker estimation were performed. Rat stomachs were collected for ulcer scoring, gene expression analysis, oxidative stress assays, histopathological and immunohistochemical examinations, and tissue eosinophil scoring. The results revealed that BV markedly decreased the ulcer index, pro-inflammatory cytokine levels, malondialdehyde levels, BAX distribution, caspase-3 expression, and tissue eosinophil levels. Additionally, significant increases in antioxidant enzymes and heat shock protein 70 localization in gastric tissue were evident following BV treatment after ASA exposure. Also, BV has been found to attenuate the haematological, haemostatic, and histopathological alterations induced by ASA. Our findings collectively indicate that the gastroprotective effect of BV against ASA-induced ulceration in rats is mediated by its antioxidant, anti-inflammatory, anti-apoptotic, and anti-secretory properties.
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Affiliation(s)
- Wafaa A Mohamed
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Yasmina M Abd-Elhakim
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
| | - Shimaa A A Ismail
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
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