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1
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Halvorsen S, Wang R, Zhang Y. Contribution of Elastic and Collagen Fibers to the Mechanical Behavior of Bovine Nuchal Ligament. Ann Biomed Eng 2023; 51:2204-2215. [PMID: 37284997 PMCID: PMC10528717 DOI: 10.1007/s10439-023-03254-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 05/16/2023] [Indexed: 06/08/2023]
Abstract
Ligamentum nuchae is a highly elastic tissue commonly used to study the structure and mechanics of elastin. This study combines imaging, mechanical testing, and constitutive modeling to examine the structural organization of elastic and collagen fibers and their contributions to the nonlinear stress-strain behavior of the tissue. Rectangular samples of bovine ligamentum nuchae cut in both longitudinal and transverse directions were tested in uniaxial tension. Purified elastin samples were also obtained and tested. It was observed that the stress-stretch response of purified elastin tissue follows a similar curve as the intact tissue initially, but the intact tissue shows a significant stiffening behavior for stretches above 1.29 with collagen engagement. Multiphoton and histology images confirm the elastin-dominated bulk of ligamentum nuchae interspersed with small bundles of collagen fibrils and sporadic collagen-rich regions with cellular components and ground substance. A transversely isotropic constitutive model that considers the longitudinal organization of elastic and collagen fibers was developed to describe the mechanical behavior of both intact and purified elastin tissue under uniaxial tension. These findings shed light on the unique structural and mechanical roles of elastic and collagen fibers in tissue mechanics and may aid in future use of ligamentum nuchae in tissue grafting.
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Affiliation(s)
- Samuel Halvorsen
- Mechanical Engineering, Boston University, 110 Cummington Mall, Boston, MA, 02215, USA
| | - Ruizhi Wang
- Mechanical Engineering, Boston University, 110 Cummington Mall, Boston, MA, 02215, USA
| | - Yanhang Zhang
- Mechanical Engineering, Boston University, 110 Cummington Mall, Boston, MA, 02215, USA.
- Biomedical Engineering, Boston University, Boston, MA, USA.
- Division of Materials Science & Engineering, Boston University, Boston, MA, USA.
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2
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Veronez A, Pires LA, de Aro AA, do Amaral MEC, Marretto Esquisatto MA. Effect of exercising in water on the fibrocartilage of the deep digital flexor tendon in rats with induced diabetes. Tissue Cell 2022; 76:101764. [DOI: 10.1016/j.tice.2022.101764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 02/19/2022] [Accepted: 02/20/2022] [Indexed: 11/29/2022]
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Eisner LE, Rosario R, Andarawis-Puri N, Arruda EM. The Role of the Non-Collagenous Extracellular Matrix in Tendon and Ligament Mechanical Behavior: A Review. J Biomech Eng 2022; 144:1128818. [PMID: 34802057 PMCID: PMC8719050 DOI: 10.1115/1.4053086] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Indexed: 12/26/2022]
Abstract
Tendon is a connective tissue that transmits loads from muscle to bone, while ligament is a similar tissue that stabilizes joint articulation by connecting bone to bone. The 70-90% of tendon and ligament's extracellular matrix (ECM) is composed of a hierarchical collagen structure that provides resistance to deformation primarily in the fiber direction, and the remaining fraction consists of a variety of non-collagenous proteins, proteoglycans, and glycosaminoglycans (GAGs) whose mechanical roles are not well characterized. ECM constituents such as elastin, the proteoglycans decorin, biglycan, lumican, fibromodulin, lubricin, and aggrecan and their associated GAGs, and cartilage oligomeric matrix protein (COMP) have been suggested to contribute to tendon and ligament's characteristic quasi-static and viscoelastic mechanical behavior in tension, shear, and compression. The purpose of this review is to summarize existing literature regarding the contribution of the non-collagenous ECM to tendon and ligament mechanics, and to highlight key gaps in knowledge that future studies may address. Using insights from theoretical mechanics and biology, we discuss the role of the non-collagenous ECM in quasi-static and viscoelastic tensile, compressive, and shear behavior in the fiber direction and orthogonal to the fiber direction. We also address the efficacy of tools that are commonly used to assess these relationships, including enzymatic degradation, mouse knockout models, and computational models. Further work in this field will foster a better understanding of tendon and ligament damage and healing as well as inform strategies for tissue repair and regeneration.
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Affiliation(s)
- Lainie E Eisner
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853
| | - Ryan Rosario
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109
| | - Nelly Andarawis-Puri
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853
| | - Ellen M Arruda
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109; Professor Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109; Professor Program in Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109
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Lu PP, Chen MH, Dai GC, Li YJ, Shi L, Rui YF. Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy. World J Stem Cells 2020; 12:1255-1275. [PMID: 33312397 PMCID: PMC7705468 DOI: 10.4252/wjsc.v12.i11.1255] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/19/2020] [Accepted: 09/10/2020] [Indexed: 02/06/2023] Open
Abstract
There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus. Diabetic tendinopathy is an important cause of chronic pain, restricted activity, and even tendon rupture in individuals. Tenocytes and tendon stem/progenitor cells (TSPCs) are the dominant cellular components associated with tendon homeostasis, maintenance, remodeling, and repair. Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy. In this review, the biomechanical properties and histopathological changes in diabetic tendons are described. Then, the cellular and molecular alterations in both tenocytes and TSPCs are summarized, and the underlying mechanisms involved are also analyzed. A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.
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Affiliation(s)
- Pan-Pan Lu
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Min-Hao Chen
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Guang-Chun Dai
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ying-Juan Li
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- 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
| | - Liu Shi
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing 210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, 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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Ribeiro Neto JA, Pimenta Tarôco BR, Batista Dos Santos H, Thomé RG, Wolfram E, Maciel de A Ribeiro RI. Using the plants of Brazilian Cerrado for wound healing: From traditional use to scientific approach. JOURNAL OF ETHNOPHARMACOLOGY 2020; 260:112547. [PMID: 31917276 DOI: 10.1016/j.jep.2020.112547] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 01/01/2020] [Accepted: 01/01/2020] [Indexed: 05/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Brazilian Cerrado is a biome with a remarkable diversity of plant species, many of which are used mainly by local communities as a source of treatment to several pathologic processes, especially for the treatment of wounds. However, no systematic review exists focusing on the plants used in this respect and on the appropriate pharmacological investigations that substantiate the actions that are reported. This study revisits the traditional use of medicinal plants from the Brazilian Cerrado in the treatment of wounds and the pharmacological characteristics of the reported plant species. METHOD ology: For the present article, previous studies on plants of the Brazilian Cerrado used for wound healing carried out between 1996 and 2018 were researched on various academic databases (PubMed, Elsevier, Springer, Lilacs, Google Escolar, and Scielo). RESULTS A total of 33 studies were carried out on 29 plant species distributed into 18 families, mainly Fabaceae or Leguminosae (9), Bignoniaceae (2), Asteraceae (2), Euphorbiaceae (2). Considering the great diversity of Cerrado plants, only a small number of wound healing studies were carried out between 1996 and 2018. It was observed that there is a large gap between experimentation assay and traditional use. There are only few connections between the form of use by the population and the experiments conducted in the laboratory. We found that only about 12% of these studies considered to use the methodologies, or at least in parts, to obtain extracts such as those used in folk medicine. Approximately 37% of the experiments were performed using the bark as well as the same ratio for leaves, 6% using the fruits, and 9% using the seeds, roots or flowers. In several studies, there are reports of chemical constituents such as flavonoids and tannins, followed by steroid terpenes, saponins, and fatty acids, and alkaloids. However, approximately 35% of the studies did not supply information about compounds present in the preparation or the effect which could be attributed to these agents in respect to wound healing. Regarding treatment, most of the studies employed a topical treatment, though intraperitoneal and oral treatment were also described using either topical, oil-based formulations, but also gel- or saline-based formulations. CONCLUSIONS Although, there has been an increase in knowledge about the biological actions of plants from Cerrado biome, the scientific basis for the traditional use of these local medicinal plants in wound healing does not provide sufficient information on the efficacy of the treatment, the molecular mechanisms, or, in particular, the effective doses used and the drug interactions. Thus, focused research investigating these hypotheses from traditional knowledge is necessary to prove the evidence of the potential pharmacological action.
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Affiliation(s)
- José Antônio Ribeiro Neto
- Universidade Federal de São João Del Rey - UFSJ - Divinópolis-MG, Rua Sebastião Gonçalves Coelho, 400, Bairro Chanadour, Cep 35.501-296, Divinópolis, MG, Brazil.
| | - Bruna Renata Pimenta Tarôco
- Universidade Federal de São João Del Rey - UFSJ - Divinópolis-MG, Rua Sebastião Gonçalves Coelho, 400, Bairro Chanadour, Cep 35.501-296, Divinópolis, MG, Brazil.
| | - Hélio Batista Dos Santos
- Universidade Federal de São João Del Rey - UFSJ - Divinópolis-MG, Rua Sebastião Gonçalves Coelho, 400, Bairro Chanadour, Cep 35.501-296, Divinópolis, MG, Brazil.
| | - Ralph Gruppi Thomé
- Universidade Federal de São João Del Rey - UFSJ - Divinópolis-MG, Rua Sebastião Gonçalves Coelho, 400, Bairro Chanadour, Cep 35.501-296, Divinópolis, MG, Brazil.
| | - Evelyn Wolfram
- Zurich University of Applied Sciences, Department of Life Sciences and Facility Management (ZHAW), CH-8820, Wädenswil, Switzerland.
| | - Rosy Iara Maciel de A Ribeiro
- Universidade Federal de São João Del Rey - UFSJ - Divinópolis-MG, Rua Sebastião Gonçalves Coelho, 400, Bairro Chanadour, Cep 35.501-296, Divinópolis, MG, Brazil.
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6
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7
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Li Y, Dai G, Shi L, Lin Y, Chen M, Li G, Rui Y. The Potential Roles of Tendon Stem/Progenitor Cells in Tendon Aging. Curr Stem Cell Res Ther 2019; 14:34-42. [PMID: 30332976 DOI: 10.2174/1574888x13666181017112233] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 09/15/2018] [Accepted: 10/02/2018] [Indexed: 12/15/2022]
Abstract
Aging is a key dangerous factor for the occurrence and severity of tendon injury, but the exact cognition of the relationship is elusive at present. More previous studies suggest age-related changes occur at tendon mechanical properties, structure and composition, but the pathological alternations may be overlooked, which might be a cause for the structure and function variations, and even speed up the progress of age-related disorders. Recently, the presence of tendon stem/progenitor cells (TSPCs) would provide new insights for the pathogenesis of tendon aging. In this review, the tendon mechanical properties, structure and composition are presented in brief, then, the pathological changes of the aging tendon are described firstly, and the latest researches on alterations of TSPCs in the pathogenesis of tendon aging have also been analyzed. At a cellular level, the hypothetical model of altered TSPCs fate for tendon aging is also proposed. Moreover, the regulation of TSPCs as a potential way of the therapies for age-related tendon diseases is discussed. Therefore, reversing the impaired function of TSPCs and promoting the tenogenic differentiation of TSPCs could become hot spots for further study and give the opportunity to establish new treatment strategies for age-related tendon injuries.
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Affiliation(s)
- Yingjuan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, China
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310000, China
| | - Guangchun Dai
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Liu Shi
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
- Program of Stem Cell and Regeneration, School of Biomedical Science, and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yucheng Lin
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Minhao Chen
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Gang Li
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
- Program of Stem Cell and Regeneration, School of Biomedical Science, and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yunfeng Rui
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310000, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
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8
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Chen B, Cheng X, Dorthe EW, Zhao Y, D'Lima D, Bydder GM, Liu S, Du J, Ma YJ. Evaluation of normal cadaveric Achilles tendon and enthesis with ultrashort echo time (UTE) magnetic resonance imaging and indentation testing. NMR IN BIOMEDICINE 2019; 32:e4034. [PMID: 30457179 DOI: 10.1002/nbm.4034] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 09/14/2018] [Accepted: 10/08/2018] [Indexed: 06/09/2023]
Abstract
Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T2 ), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3 T using novel three-dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7 T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T2 *, T1 , and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3 T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (<50 years) were investigated. On average, tendons and entheses respectively had T2 * values of 0.93 ± 0.48 ms and 2.77 ± 0.79 ms, T1 values of 644 ± 22 ms and 780 ± 55 ms, MTRs of 0.373 ± 0.03 and 0.244 ± 0.009 with an MT power of 1000° and frequency offset of 2 kHz, and macromolecular proton fractions of 18.0 ± 2.2% and 13.9 ± 1.9%. Compared with the tendon, the enthesis generally had a longer T2 *, a longer T1 , a lower MTR, and a lower macromolecular proton fraction as well as both a higher Young's modulus and stiffness. Results from this study are likely to provide a useful baseline for identifying deviations from the normal in seronegative arthritis and other disease of the entheses.
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Affiliation(s)
- Bimin Chen
- Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
- Department of Radiology, University of California, San Diego, CA, USA
| | - Xin Cheng
- Department of Radiology, University of California, San Diego, CA, USA
- Department of Histology and Embryology, Medical School, Jinan University, Guangzhou, China
| | - Erik W Dorthe
- Shiley Center for Orthopedic Research and Education at Scripps Clinic, La Jolla, CA, USA
| | - Yinghua Zhao
- Department of Radiology, University of California, San Diego, CA, USA
| | - Darryl D'Lima
- Shiley Center for Orthopedic Research and Education at Scripps Clinic, La Jolla, CA, USA
| | - Graeme M Bydder
- Department of Radiology, University of California, San Diego, CA, USA
| | - Sirun Liu
- Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jiang Du
- Department of Radiology, University of California, San Diego, CA, USA
| | - Ya-Jun Ma
- Department of Radiology, University of California, San Diego, CA, USA
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9
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Kharaz YA, Canty-Laird EG, Tew SR, Comerford EJ. Variations in internal structure, composition and protein distribution between intra- and extra-articular knee ligaments and tendons. J Anat 2018; 232:943-955. [PMID: 29498035 PMCID: PMC5978954 DOI: 10.1111/joa.12802] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2018] [Indexed: 12/11/2022] Open
Abstract
Tendons and ligaments play key roles in the musculoskeletal system in both man and animals. Both tissues can undergo traumatic injury, age‐related degeneration and chronic disease, causing discomfort, pain and increased susceptibility to wider degenerative joint disease. To date, tendon and ligament ultrastructural biology is relatively under‐studied in healthy, non‐diseased tissues. This information is essential to understand the pathology of these tissues with regard to function‐related injury and to assist with the future development of tissue‐engineered tendon and ligament structures. This study investigated the morphological, compositional and extracellular matrix protein distribution differences between tendons and ligaments around the non‐diseased canine stifle joint. The morphological, structural characteristics of different regions of the periarticular tendons and ligaments (the intra‐articular anterior cruciate ligament, the extra‐articular medial collateral ligament, the positional long digital extensor tendon and energy‐storing superficial digital flexor tendons) were identified using a novel semi‐objective histological scoring analysis and by determining their biochemical composition. Protein distribution of extracellular matrix collagens, proteoglycans and elastic fibre proteins in anterior cruciate ligament and long digital extensor tendon were also determined using immunostaining techniques. The anterior cruciate ligament was found to have significant morphological differences in comparison with the other three tissues, including less compact collagen architecture, differences in cell nuclei phenotype and increased glycosaminoglycan and elastin content. Intra‐ and interobserver differences of histology scoring resulted in an average score 0.7, indicative of good agreement between observers. Statistically significant differences were also found in the extracellular matrix composition in terms of glycosaminoglycan and elastin content, being more prominent in the anterior cruciate ligament than in the other three tissues. A different distribution of several extracellular matrix proteins was also found between long digital extensor tendon and anterior cruciate ligament, with a significantly increased immunostaining of aggrecan and versican in the anterior cruciate ligament. These findings directly relate to the different functions of tendon and ligament and indicate that the intra‐articular anterior cruciate ligament is subjected to more compressive forces, reflecting an adaptive response to normal or increased loads and resulting in different extracellular matrix composition and arrangement to protect the tissue from damage.
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Affiliation(s)
- Yalda A Kharaz
- Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
| | - Elizabeth G Canty-Laird
- Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.,The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Liverpool, UK
| | - Simon R Tew
- Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.,The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Liverpool, UK
| | - Eithne J Comerford
- Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.,The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Liverpool, UK.,Institute of Veterinary Science, University of Liverpool, Neston, UK
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10
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Fang F, Lake SP. Multiscale Mechanical Evaluation of Human Supraspinatus Tendon Under Shear Loading After Glycosaminoglycan Reduction. J Biomech Eng 2018; 139:2625661. [PMID: 28462418 DOI: 10.1115/1.4036602] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Indexed: 12/15/2022]
Abstract
Proteoglycans (PGs) are broadly distributed within many soft tissues and, among other roles, often contribute to mechanical properties. Although PGs, consisting of a core protein and glycosaminoglycan (GAG) sidechains, were once hypothesized to regulate stress/strain transfer between collagen fibrils and help support load in tendon, several studies have reported no changes to tensile mechanics after GAG depletion. Since GAGs are known to help sustain nontensile loading in other tissues, we hypothesized that GAGs might help support shear loading in human supraspinatus tendon (SST), a commonly injured tendon which functions in a complex multiaxial loading environment. Therefore, the objective of this study was to determine whether GAGs contribute to the response of SST to shear, specifically in terms of multiscale mechanical properties and mechanisms of microscale matrix deformation. Results showed that chondroitinase ABC (ChABC) treatment digested GAGs in SST while not disrupting collagen fibers. Peak and equilibrium shear stresses decreased only slightly after ChABC treatment and were not significantly different from pretreatment values. Reduced stress ratios were computed and shown to be slightly greater after ChABC treatment compared to phosphate-buffered saline (PBS) incubation without enzyme, suggesting that these relatively small changes in stress values were not due strictly to tissue swelling. Microscale deformations were also not different after ChABC treatment. This study demonstrates that GAGs possibly play a minor role in contributing to the mechanical behavior of SST in shear, but are not a key tissue constituent to regulate shear mechanics.
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Affiliation(s)
- Fei Fang
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, 1 Brookings Drive, Campus Box 1185, St. Louis, MO 63130 e-mail:
| | - Spencer P Lake
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, 1 Brookings Drive, Campus Box 1185, St. Louis, MO 63130;Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Drive, Campus Box 1185, St. Louis, MO 63130;Department of Orthopaedic Surgery, Washington University in St. Louis, 1 Brookings Drive, Campus Box 1185, St. Louis, MO 63130 e-mail:
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11
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Svensson RB, Heinemeier KM, Couppé C, Kjaer M, Magnusson SP. Effect of aging and exercise on the tendon. J Appl Physiol (1985) 2016; 121:1237-1246. [DOI: 10.1152/japplphysiol.00328.2016] [Citation(s) in RCA: 113] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 04/29/2016] [Indexed: 12/27/2022] Open
Abstract
Here, we review the literature on how tendons respond and adapt to ageing and exercise. With respect to aging, there are considerable changes early in life, but this seems to be maturation rather than aging per se. In vitro data indicate that aging is associated with a decreased potential for cell proliferation and a reduction in the number of stem/progenitor-like cells. Further, there is persuasive evidence that turnover in the core of the tendon after maturity is very slow or absent. Tendon fibril diameter, collagen content, and whole tendon size appear to be largely unchanged with aging, while glycation-derived cross-links increase substantially. Mechanically, aging appears to be associated with a reduction in modulus and strength. With respect to exercise, tendon cells respond by producing growth factors, and there is some support for a loading-induced increase in tendon collagen synthesis in humans, which likely reflects synthesis at the very periphery of the tendon rather than the core. Average collagen fibril diameter is largely unaffected by exercise, while there can be some hypertrophy of the whole tendon. In addition, it seems that resistance training can yield increased stiffness and modulus of the tendon and may reduce the amount of glycation. Exercise thereby tends to counteract the effects of aging.
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Affiliation(s)
- Rene B. Svensson
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Katja Maria Heinemeier
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
- Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; and
| | - Christian Couppé
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
- Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital, Denmark
| | - Michael Kjaer
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
- Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; and
| | - S. Peter Magnusson
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
- Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; and
- Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital, Denmark
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12
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Domnick C, Wieskötter B, Raschke MJ, Schulze M, Kronenberg D, Wefelmeier M, Langer MF, Herbort M. Evaluation of biomechanical properties: are porcine flexor tendons and bovine extensor tendons eligible surrogates for human tendons in in vitro studies? Arch Orthop Trauma Surg 2016; 136:1465-71. [PMID: 27475640 DOI: 10.1007/s00402-016-2529-2] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Porcine flexor tendons, bovine extensor tendons, and human (semitendinosus) tendons are frequently used as substitutes for human ACL grafts in biomechanical in vitro studies. This study compares the biomechanical properties and structural differences of these tendons. MATERIALS AND METHODS In this biomechanical study, fresh-frozen porcine flexor tendons, bovine extensor tendons, and human semitendinosus tendons were used (n = 36). The tendons were mounted in a uniaxial testing machine (Zwick/Roell) with cryo-clamps, leaving a 60 mm tendon part free between the two clamps. Specimens have been loaded to failure to evaluate the biomechanical parameters stiffness, yield load, and maximum load. A Total Collagen Assay Kit was used to detect differences in the total collagen type I concentration (n = 30). A one-way ANOVA was performed to detect differences in the means. The significance level was set at p < 0.05. RESULTS There were no significant differences in the stiffness between the groups (bovine 194 ± 43 N/mm, porcine 211 ± 63 N/mm, and human cadaveric 208 ± 58 N/mm). The yield and maximum loads were high (>1000 N) in all groups, but they were significantly increased in both animal specimens (means of 1681-1795 N) compared with human cadaveric specimen (means of 1289-1406 N; p < 0.01). No difference in the collagen type I concentration was detected (N.S.). CONCLUSION Porcine flexor and bovine extensor tendons are eligible substitutes with similar stiffness and high failure loads compared with human cadaveric semitendinosus tendons in in vitro studies.
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Affiliation(s)
- C Domnick
- Department of Trauma, Hand and Reconstructive Surgery, Westphalian Wilhelms University Muenster, Waldeyer Strasse 1, 48149, Muenster, Germany.
| | - B Wieskötter
- Department of Trauma, Hand and Reconstructive Surgery, Westphalian Wilhelms University Muenster, Waldeyer Strasse 1, 48149, Muenster, Germany
| | - M J Raschke
- Department of Trauma, Hand and Reconstructive Surgery, Westphalian Wilhelms University Muenster, Waldeyer Strasse 1, 48149, Muenster, Germany
| | - M Schulze
- Department of Trauma, Hand and Reconstructive Surgery, Westphalian Wilhelms University Muenster, Waldeyer Strasse 1, 48149, Muenster, Germany
| | - D Kronenberg
- Institute of Experimental Musculoskeletal Medicine, Westphalian Wilhelms University Muenster, Muenster, Germany
| | - M Wefelmeier
- Department of Operative Dentistry, Westphalian Wilhelms University Muenster, Muenster, Germany
| | - M F Langer
- Department of Trauma, Hand and Reconstructive Surgery, Westphalian Wilhelms University Muenster, Waldeyer Strasse 1, 48149, Muenster, Germany
| | - M Herbort
- Department of Trauma, Hand and Reconstructive Surgery, Westphalian Wilhelms University Muenster, Waldeyer Strasse 1, 48149, Muenster, Germany
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13
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Fang F, Lake SP. Multiscale strain analysis of tendon subjected to shear and compression demonstrates strain attenuation, fiber sliding, and reorganization. J Orthop Res 2015; 33:1704-12. [PMID: 26036894 DOI: 10.1002/jor.22955] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 05/21/2015] [Indexed: 02/04/2023]
Abstract
The manner in which strains are passed down the hierarchical length scales of tendons dictates how cells within the collagen network regulate the tissue response to loading. How tendons deform in different hierarchical levels under shear and compression is unknown. The aims of this study were: (i) to evaluate whether specific regions of bovine deep digital flexor tendons exhibited different strain attenuation from macro to micro length scales, and (ii) to elucidate mechanisms responsible for tendon deformation under shear and compression. Samples from distal and proximal regions of flexor tendons were subjected to three-step incremental stress-relaxation tests. Images of tissue markers, photobleached lines on collagen fibers, and nuclei locations were collected before and after loading. Results showed that strain transfer was attenuated from tissue to local matrix under both shear and compression. Nuclear aspect ratios exhibited smaller changes for distal samples, suggesting that cells are more shielded from deformation in the distal region. Collagen fiber sliding was observed to contribute significantly in response to shear, while uncrimping and fiber reorganization were the predominant mechanisms under compression. This study provides insight into microscale mechanisms responsible for multiscale strain attenuation of tendons under non-tensile macroscale loading.
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Affiliation(s)
- Fei Fang
- Department of Mechanical Engineering & Materials Science, Washington University, St. Louis, Missouri
| | - Spencer P Lake
- Department of Mechanical Engineering & Materials Science, Washington University, St. Louis, Missouri.,Department of Biomedical Engineering, Washington University, St. Louis, Missouri.,Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri
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14
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Hunckler MD, Tilley JMR, Roeder RK. Molecular transport in collagenous tissues measured by gel electrophoresis. J Biomech 2015; 48:4087-4092. [PMID: 26482732 DOI: 10.1016/j.jbiomech.2015.10.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/29/2015] [Accepted: 10/04/2015] [Indexed: 10/22/2022]
Abstract
Molecular transport in tissues is important for drug delivery, nutrient supply, waste removal, cell signaling, and detecting tissue degeneration. Therefore, the objective of this study was to investigate gel electrophoresis as a simple method to measure molecular transport in collagenous tissues. The electrophoretic mobility of charged molecules in tissue samples was measured from relative differences in the velocity of a cationic dye passing through an agarose gel in the absence and presence of a tissue section embedded within the gel. Differences in electrophoretic mobility were measured for the transport of a molecule through different tissues and tissue anisotropy, or the transport of different sized molecules through the same tissue. Tissue samples included tendon and fibrocartilage from the proximal (tensile) and distal (compressive) regions of the bovine flexor tendon, respectively, and bovine articular cartilage. The measured electrophoretic mobility was greatest in the compressive region of the tendon (fibrocartilage), followed by the tensile region of tendon, and lowest in articular cartilage, reflecting differences in the composition and organization of the tissues. The anisotropy of tendon was measured by greater electrophoretic mobility parallel compared with perpendicular to the predominate collagen fiber orientation. Electrophoretic mobility also decreased with increased molecular size, as expected. Therefore, the results of this study suggest that gel electrophoresis may be a useful method to measure differences in molecular transport within various tissues, including the effects of tissue type, tissue anisotropy, and molecular size.
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Affiliation(s)
- Michael D Hunckler
- Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Jennifer M R Tilley
- Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Ryan K Roeder
- Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
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15
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Ballestero Fêo H, Biancalana A, Romero Nakagaki W, Aparecida De Aro A, Gomes L. Biochemical and morphological alterations of the extracellular matrix of chicken calcaneal tendon during maturation. Microsc Res Tech 2015; 78:949-57. [DOI: 10.1002/jemt.22515] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/13/2015] [Accepted: 04/11/2015] [Indexed: 11/09/2022]
Affiliation(s)
- Haline Ballestero Fêo
- Department of Functional and Structural Biology; IB, State University of Campinas-UNICAMP; Campinas São Paulo Brazil
| | - Adriano Biancalana
- Department of Cell Biology; Federal University of Pará-UFPA; Pará Brazil
| | | | - Andrea Aparecida De Aro
- Department of Functional and Structural Biology; IB, State University of Campinas-UNICAMP; Campinas São Paulo Brazil
| | - Laurecir Gomes
- Department of Functional and Structural Biology; IB, State University of Campinas-UNICAMP; Campinas São Paulo Brazil
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16
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Ultrastructural and biochemical characterization of mechanically adaptable collagenous structures in the edible sea urchin Paracentrotus lividus. ZOOLOGY 2015; 118:147-60. [DOI: 10.1016/j.zool.2014.10.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Revised: 09/26/2014] [Accepted: 10/13/2014] [Indexed: 11/16/2022]
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17
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Svensson RB, Couppé C, Magnusson SP. Mechanical Properties of the Aging Tendon. ENGINEERING MATERIALS AND PROCESSES 2015. [DOI: 10.1007/978-3-319-03970-1_6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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18
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Fang F, Sawhney AS, Lake SP. Different regions of bovine deep digital flexor tendon exhibit distinct elastic, but not viscous, mechanical properties under both compression and shear loading. J Biomech 2014; 47:2869-77. [DOI: 10.1016/j.jbiomech.2014.07.026] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 07/16/2014] [Accepted: 07/22/2014] [Indexed: 11/30/2022]
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19
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Zorel VJ, Morais JD, de Aro AA, Gomes L, Esquisatto MAM. Effects of maturation and aging on the pressure-bearing region of the plantaris longus tendon of the bullfrog (Lithobates catesbeianus). Microsc Res Tech 2014; 77:797-805. [DOI: 10.1002/jemt.22402] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Revised: 06/19/2014] [Accepted: 07/05/2014] [Indexed: 11/07/2022]
Affiliation(s)
- Valdenilson José Zorel
- Programa de Pós-graduação em Ciências Biomédicas; Centro Universitário Hermínio Ometto, Av. Dr. Maximiliano Baruto; 500 Jd. Universitário; 13607-339 Araras SP Brazil
| | - Jymenez De Morais
- Divisão de Reumatologia; Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 Cerqueira César; 01246-903 São Paulo SP Brazil
| | - Andrea Aparecida de Aro
- Departamento de Biologia Estrutural e Funcional; Instituto de Biologia, Universidade Estadual de Campinas, Rua Charles Darwin, s/n. CxP 6109; 13083-863 Campinas SP Brazil
| | - Laurecir Gomes
- Departamento de Biologia Estrutural e Funcional; Instituto de Biologia, Universidade Estadual de Campinas, Rua Charles Darwin, s/n. CxP 6109; 13083-863 Campinas SP Brazil
| | - Marcelo Augusto Marretto Esquisatto
- Programa de Pós-graduação em Ciências Biomédicas; Centro Universitário Hermínio Ometto, Av. Dr. Maximiliano Baruto; 500 Jd. Universitário; 13607-339 Araras SP Brazil
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20
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Lanir Y. Mechanistic micro-structural theory of soft tissues growth and remodeling: tissues with unidirectional fibers. Biomech Model Mechanobiol 2014; 14:245-66. [DOI: 10.1007/s10237-014-0600-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 05/23/2014] [Indexed: 10/25/2022]
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21
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Sutured tendon repair; a multi-scale finite element model. Biomech Model Mechanobiol 2014; 14:123-33. [PMID: 24840732 PMCID: PMC4282689 DOI: 10.1007/s10237-014-0593-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 05/05/2014] [Indexed: 12/12/2022]
Abstract
Following rupture, tendons are sutured to reapproximate the severed ends and permit healing. Several repair techniques are employed clinically, with recent focus towards high-strength sutures, permitting early active mobilisation thus improving resultant joint mobility. However, the arrangement of suture repairs locally alters the loading environment experienced by the tendon. The extent of the augmented stress distribution and its effect on the tissue is unknown. Stress distribution cannot be established using traditional tensile testing, in vivo, or ex vivo study of suture repairs. We have developed a 3D finite element model of a Kessler suture repair employing multiscale modelling to represent tendon microstructure and incorporate its highly orthotropic behaviour into the tissue description. This was informed by ex vivo tensile testing of porcine flexor digitorum profundus tendon. The transverse modulus of the tendon was 0.2551 \documentclass[12pt]{minimal}
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\begin{document}$$\pm $$\end{document}± 0.0454 MPa in proximal and distal tendon samples, respectively, and the interfibrillar tissue modulus ranged from 0.1021 to 0.0416 MPa. We observed an elliptically shaped region of high stress around the suture anchor, consistent with a known region of acellularity which develop 72 h post-operatively and remain for at least a year. We also observed a stress shielded region close to the severed tendon ends, which may impair collagen fibre realignment during the remodelling stage of repair due to the lack of tensile stress.
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22
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Cheng CW, Solorio LD, Alsberg E. Decellularized tissue and cell-derived extracellular matrices as scaffolds for orthopaedic tissue engineering. Biotechnol Adv 2014; 32:462-84. [PMID: 24417915 PMCID: PMC3959761 DOI: 10.1016/j.biotechadv.2013.12.012] [Citation(s) in RCA: 255] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Revised: 12/27/2013] [Accepted: 12/31/2013] [Indexed: 02/07/2023]
Abstract
The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic.
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Affiliation(s)
- Christina W Cheng
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Wickenden Building, Rm 218, Cleveland, OH, USA; Department of Orthopaedic Surgery, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, USA.
| | - Loran D Solorio
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Wickenden Building, Rm 218, Cleveland, OH, USA.
| | - Eben Alsberg
- Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Wickenden Building, Rm 218, Cleveland, OH, USA; Department of Orthopaedic Surgery, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, USA; National Center for Regenerative Medicine, Division of General Medical Sciences, Case Western Reserve University, Cleveland, OH, USA.
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23
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Misty Paig-Tran EW, Summers AP. Comparison of the structure and composition of the branchial filters in suspension feeding elasmobranchs. Anat Rec (Hoboken) 2014; 297:701-15. [PMID: 24443216 DOI: 10.1002/ar.22850] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Accepted: 11/05/2013] [Indexed: 11/12/2022]
Abstract
The four, evolutionarily independent, lineages of suspension feeding elasmobranchs have two types of branchial filters. The first is a robust, flattened filter pad akin to a colander (e.g., whale sharks, mantas and devil rays) while the second more closely resembles the comb-like gill raker structure found in bony fishes (e.g., basking and megamouth sharks). The structure and the presence of mucus on the filter elements will determine the mechanical function of the filter and subsequent particle transport. Using histology and scanning electron microscopy, we investigated the anatomy of the branchial filters in 12 of the 14 species of Chondrichthyian filter-feeding fishes. We hypothesized that mucus producing cells would be abundant along the filter epithelium and perform as a sticky mechanism to retain and transport particles; however, we found that only three species had mucus producing goblet cells. Two of these (Mobula kuhlii and Mobula tarapacana) also had branchial cilia, indicating sticky retention and transport. The remaining filter-feeding elasmobranchs did not have a sticky surface along the filter for particles to collect and instead must employ alternative mechanisms of filtration (e.g., direct sieving, inertial impaction or cross-flow). With the exception of basking sharks, the branchial filter is composed of a hyaline cartilage skeleton surrounded by a layer of highly organized connective tissue that may function as a support. Megamouth sharks and most of the mobulid rays have denticles along the surface of the filter, presumably to protect against damage from large particle impactions. Basking sharks have branchial filters that lack a cartilaginous core; instead they are composed entirely of smooth keratin.
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Affiliation(s)
- E W Misty Paig-Tran
- Friday Harbor Laboratories, University of Washington, Friday Harbor, Washington
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24
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Abstract
CONTEXT Aging changes the biology, healing capacity, and biomechanical function of tendons and ligaments and results in common clinical pathologies that present to orthopedic surgeons, primary care physicians, physical therapists, and athletic trainers. A better understanding of the age-related changes in these connective tissues will allow better patient care. EVIDENCE ACQUISITION The PubMed database was searched in December 2012 for English-language articles pertaining to age-related changes in tendons and ligaments. LEVEL OF EVIDENCE Level 5. RESULTS The mature athlete faces challenges associated with age-dependent changes in the rotator cuff, Achilles tendon, lateral humeral epicondylar tendons, quadriceps tendon, and patellar tendon. The anterior cruciate ligament and the medial collateral ligament are the most studied intra-articular and extra-articular ligaments, and both are associated with age-dependent changes. CONCLUSION Tendons and ligaments are highly arranged connective tissue structures that maintain joint motion and joint stability. These structures are subject to vascular and compositional changes with increasing age that alter their mechanotransduction, biology, healing capacity, and biomechanical function. Emerging research into the etiology of age-dependent changes will provide further information to help combat the age-related clinical complications associated with the injuries that occur to tendons and ligaments.
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25
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Thompson MS. Tendon mechanobiology: experimental models require mathematical underpinning. Bull Math Biol 2013; 75:1238-54. [PMID: 23681792 DOI: 10.1007/s11538-013-9850-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Accepted: 04/25/2013] [Indexed: 10/26/2022]
Abstract
Mathematical and computational modeling is in demand to help address current challenges in mechanobiology of musculoskeletal tissues. In particular for tendon, the high clinical importance of the tissue, the huge mechanical demands placed on it and its ability to adapt to these demands, require coupled, multiscale models incorporating complex geometrical and microstructural information as well as time-based descriptions of cellular activity and response.This review introduces the information sources required to develop such multiscale models. It covers tissue structure and biomechanics, cell biomechanics, the current understanding of tendon's ability in health and disease to update its properties and structure and the few already existing multiscale mechanobiological models of the tissue. Finally, a sketch is provided of what such models could achieve ideally, pointing out where experimental data and knowledge are still missing.
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Affiliation(s)
- Mark S Thompson
- Institute of Biomedical Engineering, Botnar Research Centre, University of Oxford, Windmill Road, Oxford, OX3 7LD, UK.
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26
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Vanderploeg EJ, Wilson CG, Imler SM, Ling CHY, Levenston ME. Regional variations in the distribution and colocalization of extracellular matrix proteins in the juvenile bovine meniscus. J Anat 2012; 221:174-86. [PMID: 22703476 DOI: 10.1111/j.1469-7580.2012.01523.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
A deeper understanding of the composition and organization of extracellular matrix molecules in native, healthy meniscus tissue is required to fully appreciate the degeneration that occurs in joint disease and the intricate environment in which an engineered meniscal graft would need to function. In this study, regional variations in the tissue-level and pericellular distributions of collagen types I, II and VI and the proteoglycans aggrecan, biglycan and decorin were examined in the juvenile bovine meniscus. The collagen networks were extensively, but not completely, colocalized, with tissue-level organization that varied with radial position across the meniscus. Type VI collagen exhibited close association with large bundles composed of type I and II collagen and, in contrast to type I and II collagen, was further concentrated in the pericellular matrix. Aggrecan was detected throughout the inner region of the meniscus but was restricted to the pericellular matrix and sheaths of collagen bundles in the middle and outer regions. The small proteoglycans biglycan and decorin exhibited regional variations in staining intensity but were consistently localized in the intra- and/or peri-cellular compartments. These results provide insight into the complex hierarchy of extracellular matrix organization in the meniscus and provide a framework for better understanding meniscal degeneration and disease progression and evaluating potential repair and regeneration strategies.
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Affiliation(s)
- Eric J Vanderploeg
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
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Mechanics and kinematics of soft tissue under indentation are determined by the degree of initial collagen fiber alignment. J Mech Behav Biomed Mater 2012; 13:25-35. [PMID: 22842273 DOI: 10.1016/j.jmbbm.2012.03.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Revised: 03/15/2012] [Accepted: 03/28/2012] [Indexed: 11/20/2022]
Abstract
While several studies have evaluated how the degree of collagen alignment affects the response of soft tissues to tensile loading, the role of fibrillar organization in indentation is less understood. Collagen-based tissue-equivalents (TEs) provide a convenient model system to explore structure-function relationships since their microstructural properties can be easily controlled during fabrication. The purpose of this study was to evaluate the role of initial collagen alignment on the mechanical and structural behavior of soft tissues subjected to indentation using TEs as a model system. Cell-compacted TEs with either isotropic or highly anisotropic fiber alignment were subjected to four-step incremental stress-relaxation indentation tests. The mechanical properties, collagen reorganization and 2D strain patterns were quantified at each indentation step and compared between groups. While no differences were seen in the peak force response, significant differences were seen in relaxation behavior, fiber kinematics and tissue strain. Specifically, highly aligned samples exhibited a slower relaxation rate, smaller changes in collagen fiber orientation, larger changes in strength of alignment, and larger strain magnitudes compared to isotropic samples. Results demonstrate the significant role that microstructural organization plays in mediating the response of soft tissues to a non-tensile (i.e., indentation) mechanical stimulus.
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28
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Wang VM, Bell RM, Thakore R, Eyre DR, Galante JO, Li J, Sandy JD, Plaas A. Murine tendon function is adversely affected by aggrecan accumulation due to the knockout of ADAMTS5. J Orthop Res 2012; 30:620-6. [PMID: 21928430 DOI: 10.1002/jor.21558] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2011] [Accepted: 08/24/2011] [Indexed: 02/04/2023]
Abstract
The present study examined the effect of ADAMTS5 (TS5) knockout on the properties of murine flexor digitorum longus (FDL) and Achilles tendons. FDL and Achilles tendons were analyzed using biomechanical testing, histology, and immunohistochemistry; further characterization of FDL tendons was conducted using transmission electron microscopy (collagen fibril ultrastructure), SDS-PAGE (collagen content and type), fluorescence-assisted carbohydrate electrophoresis for chondroitin sulfate and hyaluronan, and Western blotting for aggrecan, versican, and decorin abundance and distribution. FDL tendons of TS5(-/-) mice showed a 33% larger cross-sectional area, increased collagen fibril area fraction, and decreased material properties relative to those of wild type mice. In TS5(-/-) mice, aggrecan accumulated in the pericellular matrix of tendon fibroblasts. In Achilles tendons, cross-sectional area, stress relaxation, and structural properties were similar in TS5(-/-) and wild type mice; however, the TS5(-/-) tendons exhibited a higher tensile modulus and a weakened enthesis. These results demonstrate that TS5 deficiency disturbs normal tendon collagen organization and alters biomechanical properties. Hence, the role of ADAMTS5 in tendon is to remove pericellular and interfibrillar aggrecan to maintain the molecular architecture responsible for normal tissue function.
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Affiliation(s)
- Vincent M Wang
- Departments of Orthopedic Surgery, Rheumatology/Internal Medicine, and Biochemistry, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois 60612, USA.
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The role of mechanobiology in tendon healing. J Shoulder Elbow Surg 2012; 21:228-37. [PMID: 22244066 PMCID: PMC3259533 DOI: 10.1016/j.jse.2011.11.002] [Citation(s) in RCA: 167] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Revised: 11/11/2011] [Accepted: 11/12/2011] [Indexed: 02/01/2023]
Abstract
Mechanical cues affect tendon healing, homeostasis, and development in a variety of settings. Alterations in the mechanical environment are known to result in changes in the expression of extracellular matrix proteins, growth factors, transcription factors, and cytokines that can alter tendon structure and cell viability. Loss of muscle force in utero or in the immediate postnatal period delays tendon and enthesis development. The response of healing tendons to mechanical load varies depending on anatomic location. Flexor tendons require motion to prevent adhesion formation, yet excessive force results in gap formation and subsequent weakening of the repair. Excessive motion in the setting of anterior cruciate ligament reconstruction causes accumulation of macrophages, which are detrimental to tendon graft healing. Complete removal of load is detrimental to rotator cuff healing; yet, large forces are also harmful. Controlled loading can enhance healing in most settings; however, a fine balance must be reached between loads that are too low (leading to a catabolic state) and too high (leading to microdamage). This review will summarize existing knowledge of the mechanobiology of tendon development, homeostasis, and healing.
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Lake SP, Hald ES, Barocas VH. Collagen-agarose co-gels as a model for collagen-matrix interaction in soft tissues subjected to indentation. J Biomed Mater Res A 2011; 99:507-15. [PMID: 21913316 PMCID: PMC3206166 DOI: 10.1002/jbm.a.33183] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Revised: 05/11/2011] [Accepted: 06/01/2011] [Indexed: 11/08/2022]
Abstract
The mechanical properties of soft tissues depend on the collagen fiber network and the surrounding non-fibrillar matrix. The mechanical role of non-fibrillar material remains poorly understood. Our recent study (Lake and Barocas, Ann Biomed Eng 2011) introduced collagen-agarose co-gels as a simple experimental model system to evaluate the mechanical contribution of non-fibrillar matrix, and evaluated co-gel properties in uniaxial tension. In this study, we utilized similar co-gels to examine collagen-matrix interaction in tissues subjected to incremental stress-relaxation indentation tests. Mechanical testing was performed using two orthogonal custom test devices, and polarized light imaging was used to quantify 3D collagen fiber kinematics under load. The addition of agarose led to concentration-dependent changes in the time-dependent mechanical response and magnitude/spread of collagen fiber reorganization of tissue analogs. Specifically, peak/relaxed loads increased, and relaxation rate decreased, with increasing agarose concentration. In addition, increasing agarose content led to larger magnitude changes in orientation direction and alignment strength that were more localized near the indenter. Results suggest that non-fibrillar material significantly contributes to the behavior of co-gels in indentation, likely by reducing permeability and resisting volume change, thereby providing insight into the properties of artificial and native tissues subjected to non-tensile loading.
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Affiliation(s)
- Spencer P Lake
- Department of Biomedical Engineering, University of Minnesota, Minnesota, USA
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de Aro AA, Vidal BDC, Biancalana A, Tolentino FT, Gomes L, Mattiello SM, Pimentel ER. Analysis of the deep digital flexor tendon in rats submitted to stretching after immobilization. Connect Tissue Res 2011; 53:29-38. [PMID: 21967646 DOI: 10.3109/03008207.2011.608868] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Few studies have analyzed the effect of stretching after immobilization on the structural and biochemical properties of tendons. Here, the effect of stretching and immobilization on the proximal (p), intermediate (i), and distal (d) regions of the deep digital flexor tendon in rats was analyzed. The d region was subjected to compression and tension forces, the i region was subjected to compressive forces and the p region received tension forces. Rats were separated into five groups: GI--control for GII; GII--immobilized rats; GIII--control for GIV and GV groups; GIV--immobilized and stretched rats; and GV--immobilized rats which were allowed free cage activity. GII showed a higher molecular organization in the d and p regions as detected by measuring optical retardation, a lower concentration of hydroxyproline in the i region and a significant decrease in noncollagenous proteins found in the three regions of the tendon. Regarding the glycosaminoglycans, diminishing dermatan sulfate and the absence of chondroitin sulfate in the i region were observed in GII when compared to GI. However, in the same region of GIV, higher concentrations of chondroitin and dermatan sulfate were observed along with a strong metachromasy. An increase in hydroxyproline content in the i region and a higher molecular organization in the d and p regions were observed in GIV. Apparently, the active isoforms of metalloproteinase-2 also increased after stretching in all regions. These results suggest that stretching after immobilization contributed to the increase in molecular organization and to the synthesis of extracellular matrix components.
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Affiliation(s)
- Andrea Aparecida de Aro
- Department of Anatomy, Cell Biology, Physiology and Biophysics, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
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Effects of stretching on morphological and biochemical aspects of the extracellular matrix of the rat calcaneal tendon. Cell Tissue Res 2010; 342:97-105. [PMID: 20809413 DOI: 10.1007/s00441-010-1027-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2010] [Accepted: 07/23/2010] [Indexed: 10/19/2022]
Abstract
Several studies have demonstrated the relationship between exercise and the extracellular matrix of muscle tendons, and have described alterations in their structural and biochemical properties when subjected to strenuous exercise. However, little is known about what happens to tendons when they are subjected to stretching. We evaluated the changes in the composition and structure of rat calcaneal tendons subjected to a stretching program. The animals had their muscles stretched for 30 s with 30 s of rest, with 10 repetitions, three and five times a week for 21 days. For morphological analysis, the sections were stained with hematoxylin-eosin and toluidine blue. For biochemical analysis, the tendons were treated with 4 M guanidine hydrochloride and analyzed in SDS-PAGE. The contents of total proteins and glycosaminoglycans were also measured. In the sections stained with toluidine blue, we could observe an increase of rounded cells, especially in the enthesis region. In the region next to the enthesis was a metachromatic region, which was more intensely stained in the stretched groups. In the tension regions, the cells appeared more aligned. Cellularity increased in both regions. The SDS-PAGE analysis showed a larger amount of collagen in the stretched groups and a polydispersed component of 65 kDa in all the groups. The amounts of proteins and glycosaminoglycans were also larger in the stretched tendons. The agarose-gel electrophoresis confirmed the presence of dermatan sulfate in the tension and compression regions, and of chondroitin sulfate only in the latter. Our results showed that the stretching stimulus changed the cellularity and the amount of the extracellular matrix compounds, confirming that tendons are dynamic structures with a capacity to detect alterations in their load.
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Local strain measurement reveals a varied regional dependence of tensile tendon mechanics on glycosaminoglycan content. J Biomech 2009; 42:1547-1552. [DOI: 10.1016/j.jbiomech.2009.03.031] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2008] [Revised: 03/16/2009] [Accepted: 03/17/2009] [Indexed: 11/24/2022]
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Lujan TJ, Underwood CJ, Jacobs NT, Weiss JA. Contribution of glycosaminoglycans to viscoelastic tensile behavior of human ligament. J Appl Physiol (1985) 2008; 106:423-31. [PMID: 19074575 DOI: 10.1152/japplphysiol.90748.2008] [Citation(s) in RCA: 105] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
The viscoelastic properties of human ligament potentially guard against structural failure, yet the microstructural origins of these transient behaviors are unknown. Glycosaminoglycans (GAGs) are widely suspected to affect ligament viscoelasticity by forming molecular bridges between neighboring collagen fibrils. This study investigated whether GAGs directly affect viscoelastic material behavior in human medial collateral ligament (MCL) by using nondestructive tensile tests before and after degradation of GAGs with chondroitinase ABC (ChABC). Control and ChABC treatment (83% GAG removal) produced similar alterations to ligament viscoelasticity. This finding was consistent at different levels of collagen fiber stretch and tissue hydration. On average, stress relaxation increased after incubation by 2.2% (control) and 2.1% (ChABC), dynamic modulus increased after incubation by 3.6% (control) and 3.8% (ChABC), and phase shift increased after incubation by 8.5% (control) and 8.4% (ChABC). The changes in viscoelastic behavior after treatment were significantly more pronounced at lower clamp-to-clamp strain levels. A 10% difference in the water content of tested specimens had minor influence on ligament viscoelastic properties. The major finding of this study is that mechanical interactions between collagen fibrils and GAGs are unrelated to tissue-level viscoelastic mechanics in mature human MCL. These findings narrow the possible number of extracellular matrix molecules that have a direct contribution to ligament viscoelasticity.
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Affiliation(s)
- Trevor J Lujan
- Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA
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35
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Aro AA, Vidal BC, Tomiosso TC, Gomes L, Matiello-Rosa SMG, Pimentel ER. Structural and biochemical analysis of the effect of immobilization followed by stretching on the calcaneal tendon of rats. Connect Tissue Res 2008; 49:443-54. [PMID: 19085245 DOI: 10.1080/03008200802325250] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Little is known about the stretching effects on the biochemical and morphological features of tendons submitted to a long period of immobilization. Our purpose was to evaluate the response of rat tendons to stretching procedures after immobilization. The animals were separated into five experimental groups: GI--control of immobilized and euthanized animals; GII--immobilized and euthanized animals; GIII--control of immobilized animals and afterward stretched or allowed free cage activity; GIV--immobilized and stretched animals; and GV--immobilized and allowed free cage activity. Analysis in SDS-PAGE showed no remarkable differences among the groups, but a prominent collagen band was observed in GV, as compared to GIV and the control group, both in the compression and tension regions. Hydroxyproline content was highest in the compression region of GII. No differences among the groups were observed in the tension region. In regard to the concentration of noncollagenous proteins, differences were detected only in the tension region, where larger concentrations were found in the GII. When GII and GIV were compared, highest values were found in the GII. A more abundant presence of sulfated glycosaminoglycans, especially chondroitin sulfate, was detected in GIV, at the compression region of tendons. The presence of dermatan sulfate was outstanding in the compression and tension regions of the GII and GV groups. In the Ponceau SS stained sections, analyzed under polarization microscopy, GII exhibited the highest disorganization of the collagen bundles, partially recovered after stretching or with only remobilization. Our results indicate that a revision in the stretching procedures, in terms of duration and periodicity of the sessions, could benefit the efficiency of the stretching in cases of previous immobilization of tendons.
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Affiliation(s)
- Andrea A Aro
- Department of Cell Biology, State University of Campinas, Campinas, SP, Brazil
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36
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Moussa M, Swider P, Babilé R, Fernandez X, Rémignon H. Effects of physical activities on biochemical and biomechanical properties of tendons in two commercial types of chickens. Connect Tissue Res 2008; 49:76-84. [PMID: 18382893 DOI: 10.1080/03008200801913593] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The aim of our experiment was to study the effects of physical activities on the biochemical and biomechanical properties of tendons in 12 standard (S) broilers and 12 Label Rouge (LR) chickens. In the two types of birds no differences were found between control and active birds for body weights. Gastrocnemius (Gas) tendon and Pectoralis minor (Pm) tendons were harvested and processed for passive stretch tests prior to cooking or not. Some biochemical parameters also were determined. Results showed that total collagen content in Gas tendon was significantly higher in active than in control birds. However, no significant changes were found in collagen solubility in LR tendons while these values were increased in S ones. Active birds showed greater sGAGs content than control ones. Ultimate load was found to be significantly higher in active birds than in control. Deformability (defined by Poisson's ratio) of raw and heated at 80 degrees C Gas tendons increases in active groups because Poisson's ratio decreases. Physical activities also increase the rigidity (defined by elastic modulus) of raw and heated at 80 degrees C Gas tendons because elastic modulos values increase. Physical activity was not able to modify stiffness or maximum stress values in raw or heated at 80 degrees C Gas tendons from broilers whereas these two parameters were found to be slightly higher in active group from LR chickens only in raw tendons. All the biomechanical results recorded in Pm tendons from both types of chickens were not significantly different between control and active birds. A significant correlation was found between the total collagen content and stiffness in Gas tendon from LR active birds.
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Affiliation(s)
- Majed Moussa
- Tissus Animaux, Nutrition, Digestion, Ecosystéme et Métabolisme, Université de Toulouse, Cedex, France
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37
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Extracellular matrix of porcine pericardium: biochemistry and collagen architecture. J Membr Biol 2007; 221:15-25. [PMID: 18060343 DOI: 10.1007/s00232-007-9081-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2007] [Accepted: 10/09/2007] [Indexed: 10/22/2022]
Abstract
Pericardial tissue has been used to construct bioprostheses employed in the repair of different kinds of injuries, mostly cardiac. However, calcification and mechanical failure have been the main causes of the limited durability of cardiac bioprostheses constructed with bovine pericardium. In the course of this work, a study was conducted on porcine fibrous pericardium, its microscopic structure and biochemical nature. The general morphology and architecture of collagen were studied under conventional light and polarized light microscopy. The biochemical study of the pericardial matrix was conducted according to the following procedures: swelling test, hydroxyproline and collagen dosage, quantification of amino acids in soluble collagen, component extraction of the extracellular matrix of the right and left ventral regions of pericardium with different molarities of guanidine chloride, protein and glycosaminoglycan (GAG) dosage, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and total GAG analysis. Microscopic analysis showed collagen fibers arranged in multidirectionally oriented layers forming a closely knit web, with a larger number of fibers obliquely oriented, initiating at the lower central region toward the upper left lateral relative to the heart. No qualitative differences were found between proteins extracted from the right and left regions. Likewise, no differences were found between fresh and frozen material. Protein dosages from left frontal and right frontal pericardium regions showed no significant differences. The quantities of extracted GAGs were too small for detection by the method used. Enzymatic digestion and electrophoretic analysis showed that the GAG found is possibly dermatan sulfate. The proteoglycan showed a running standard very similar to the small proteoglycan decorin.
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38
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Evanko SP, Tammi MI, Tammi RH, Wight TN. Hyaluronan-dependent pericellular matrix. Adv Drug Deliv Rev 2007; 59:1351-65. [PMID: 17804111 PMCID: PMC2174428 DOI: 10.1016/j.addr.2007.08.008] [Citation(s) in RCA: 215] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2007] [Revised: 07/25/2007] [Accepted: 08/01/2007] [Indexed: 12/12/2022]
Abstract
Hyaluronan is a multifunctional glycosaminoglycan that forms the structural basis of the pericellular matrix. Hyaluronan is extruded directly through the plasma membrane by one of three hyaluronan synthases and anchored to the cell surface by the synthase or cell surface receptors such as CD44 or RHAMM. Aggregating proteoglycans and other hyaluronan-binding proteins, contribute to the material and biological properties of the matrix and regulate cell and tissue function. The pericellular matrix plays multiple complex roles in cell adhesion/de-adhesion, and cell shape changes associated with proliferation and locomotion. Time-lapse studies show that pericellular matrix formation facilitates cell detachment and mitotic cell rounding. Hyaluronan crosslinking occurs through various proteins, such as tenascin, TSG-6, inter-alpha-trypsin inhibitor, pentraxin and TSP-1. This creates higher order levels of structured hyaluronan that may regulate inflammation and other biological processes. Microvillous or filopodial membrane protrusions are created by active hyaluronan synthesis, and form the scaffold of hyaluronan coats in certain cells. The importance of the pericellular matrix in cellular mechanotransduction and the response to mechanical strain are also discussed.
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Affiliation(s)
- Stephen P. Evanko
- The Hope Heart Program, Benaroya Research Institute at Virginia Mason, 1201 9 Avenue, Seattle, WA 98101, USA
| | - Markku I. Tammi
- Department of Anatomy, Kuopio University, FIN-70211 Kuopio, Finland
| | - Raija H. Tammi
- Department of Anatomy, Kuopio University, FIN-70211 Kuopio, Finland
| | - Thomas N. Wight
- The Hope Heart Program, Benaroya Research Institute at Virginia Mason, 1201 9 Avenue, Seattle, WA 98101, USA
- *Correspondence: Thomas N. Wight, The Hope Heart Program, Benaroya Research Institute at Virginia Mason, 1201 9 Avenue, Seattle, WA 98101, , Phone: (206) 341-1377, Fax: (206) 341-1370
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Feitosa VLC, Reis FP, Esquisatto MAM, Joazeiro PP, Vidal BC, Pimentel ER. Comparative ultrastructural analysis of different regions of two digital flexor tendons of pigs. Micron 2006; 37:518-25. [PMID: 16546397 DOI: 10.1016/j.micron.2006.01.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2005] [Accepted: 01/17/2006] [Indexed: 10/25/2022]
Abstract
Tendons are parallel arrays of collagenous fibers which are specialized in resisting and transmitting tensile forces. In this work we examined the structure of the superficial digital flexor tendon (SDFT) and the deep digital flexor tendon (DDFT) of pigs, which are considered "wrap around" tendons and so receive compression and tension forces. In both tendons, fibrocartilaginous areas were observed in the regions subjected to compression plus frictional loading. Histological and ultrastructural analyses of the tensional region showed an extracellular matrix (ECM) rich in collagen bundles, that were all arranged in the same direction. Fibroblasts were seen closely associated with the collagen bundles. Chondrocyte-like cells and high levels of glycosaminoglycans (GAGs) were observed in the compressional regions. The collagen bundles in the compressional region were arranged in several directions and were associated with proteoglycans (PGs). The crimp pattern detected in the tensional region showed that the collagen fibrils were ordered aggregates which formed helical superstructures.
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Affiliation(s)
- V L C Feitosa
- Department of Morphology, Federal University of Sergipe, Aracaju, SE, Brazil
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40
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Porter ME, Beltrán JL, Koob TJ, Summers AP. Material properties and biochemical composition of mineralized vertebral cartilage in seven elasmobranch species (Chondrichthyes). J Exp Biol 2006; 209:2920-8. [PMID: 16857876 DOI: 10.1242/jeb.02325] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
SUMMARY
Elasmobranchs, particularly sharks, function at speed and size extremes,exerting large forces on their cartilaginous skeletons while swimming. This casts doubt on the generalization that cartilaginous skeletons are mechanically inferior to bony skeletons, a proposition that has never been experimentally verified. We tested mineralized vertebral centra from seven species of elasmobranch fishes: six sharks and one axially undulating electric ray. Species were chosen to represent a variety of morphologies, inferred swimming speeds and ecological niches. We found vertebral cartilage to be as stiff and strong as mammalian trabecular bone. Inferred swimming speed was a good, but not infallible, predictor of stiffness and strength. Collagen content was also a good predictor of material stiffness and strength, although proteoglycan was not. The mineral fraction in vertebral cartilage was similar to that in mammalian trabecular bone and was a significant predictor of material properties.
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Affiliation(s)
- Marianne E Porter
- Department of Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, CA 92697-2525, USA.
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41
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Abstract
Tendons are able to respond to mechanical forces by altering their structure, composition, and mechanical properties--a process called tissue mechanical adaptation. The fact that mechanical adaptation is effected by cells in tendons is clearly understood; however, how cells sense mechanical forces and convert them into biochemical signals that ultimately lead to tendon adaptive physiological or pathological changes is not well understood. Mechanobiology is an interdisciplinary study that can enhance our understanding of mechanotransduction mechanisms at the tissue, cellular, and molecular levels. The purpose of this article is to provide an overview of tendon mechanobiology. The discussion begins with the mechanical forces acting on tendons in vivo, tendon structure and composition, and its mechanical properties. Then the tendon's response to exercise, disuse, and overuse are presented, followed by a discussion of tendon healing and the role of mechanical loading and fibroblast contraction in tissue healing. Next, mechanobiological responses of tendon fibroblasts to repetitive mechanical loading conditions are presented, and major cellular mechanotransduction mechanisms are briefly reviewed. Finally, future research directions in tendon mechanobiology research are discussed.
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Affiliation(s)
- James H-C Wang
- MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, 210 Lothrop St., BST, E1647, Pittsburgh, PA 15213, USA.
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42
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Yokota A, Gimbel JA, Williams GR, Soslowsky LJ. Supraspinatus tendon composition remains altered long after tendon detachment. J Shoulder Elbow Surg 2005; 14:72S-78S. [PMID: 15726090 DOI: 10.1016/j.jse.2004.09.021] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Most rotator cuff surgery is performed on chronic tears, but changes in the composition of chronically torn tendons remain poorly understood. In this study we surgically created supraspinatus tears in the rat and analyzed the composition of the tendon over time using immunohistochemistry. We found that collagen types I and XII were greatly increased initially after injury and then decreased with time. Collagen type III was detected and persisted in the scar for months. Decorin and biglycan were increased initially and then decreased, although decorin remained elevated from normal for months after injury. Aggrecan and collagen type II were detected in small amounts after detachment, which was associated with the expression of sulfated glycosaminoglycans. These alterations were similar to those seen in human studies. As the quality of the tendon is an important factor in repair, these findings may partially explain why chronic tears heal differently than acute tears.
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Affiliation(s)
- Atsushi Yokota
- McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA
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43
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Baker AR, Abreu EL, Mascha E, Derwin KA. Homotypic variation of canine flexor tendons: implications for the design of experimental studies in animal models. J Biomech 2004; 37:959-68. [PMID: 15165866 DOI: 10.1016/j.jbiomech.2003.11.029] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2003] [Indexed: 11/30/2022]
Abstract
Water, collagen and glycosamimoglycan contents, cross-sectional area, stiffness and elastic modulus were carefully quantitated in flexor digitorum superficialis tendons from mature canines. From these data the within- and between-animal variability was estimated and used to demonstrate sample size calculations for both two-group and paired (within-animal) study designs. The estimated between-dog variance was typically 50% or less of the total variance for the parameters investigated. In other words, the correlation among the tendons within an animal for most measures was not strong. Therefore, for some variables (e.g., elastic modulus) in this animal and tendon model, there is no appreciable gain in statistical power by using a paired study design. A two-group design could be used, but any within-animal correlation must be accounted for in the analysis. For other variables such as collagen content, a paired design would gain substantial power.
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Affiliation(s)
- A R Baker
- Department of Biomedical Engineering and the Orthopaedic Research Center, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195-5254, USA
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44
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Affiliation(s)
- G Riley
- Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge CB2 2NH, UK
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45
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Benevides G, Pimentel E, Toyama M, Novello JC, Marangoni S, Gomes L. Biochemical and biomechanical analysis of tendons of caged and penned chickens. Connect Tissue Res 2004; 45:206-15. [PMID: 15763929 DOI: 10.1080/03008200490522997] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Chickens were divided into two groups, one caged and the other penned. Superficial digital flexor tendons from penned chickens showed greater tensile strength, withstanding a greater strain before rupture than tendons from caged chickens. The tensile region of tendons from penned chickens showed more swelling in acetic acid and a higher hydroxyproline concentration compared with caged chickens, indicating the presence of large collagen amounts in the former. The tensile region of penned chickens presented higher glycosaminoglycan concentrations than the same region of caged chickens. For both groups, the predominant glycosaminoglycan in the compression regions was chondroitin sulfate, whereas dermatan sulfate was found in the tensile regions. N-terminal analysis identified the small proteoglycans fibromodulin and decorin. SDS-PAGE indicated that decorin was present in all regions and fibromodulin was mainly observed in the tensile region. These results indicate that an external condition, in this case the area available for locomotion, might influence the synthesis of extracellular matrix components and the mechanical properties of the tendon.
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Affiliation(s)
- Gustavo Benevides
- Department of Cell Biology, Institute of Biology, State University of Campinas, Campinas, São Paulo, Brazil
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Moore JS. Biomechanical models for the pathogenesis of specific distal upper extremity disorders. Am J Ind Med 2002; 41:353-69. [PMID: 12071489 DOI: 10.1002/ajim.10037] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Knowledge of the pathogenesis of most disorders that occur in the distal upper extremity is generally lacking. The individual roles of postulated etiologic factors, such as biomechanical or psychosocial exposures, are poorly understood and their potential interactions even less so. This article proposes biomechanical or physiological models of pathogenesis for specific distal upper extremity disorders. METHODS Tendon entrapment of the dorsal wrist compartments (tenosynovitis), peritendinitis, lateral epicondylitis, and carpal tunnel syndrome are common specific neuromusculoskeletal disorders of the upper extremities observed among workers. The normal anatomy and function of the targeted structures is considered the initial state; their pathology is considered the final state. Using biomechanical or physiological principles combined with clinical observations and experimental studies, pathways leading from the initial state to the final state are proposed. Each model defined a critical biomechanical or physiological attribute that was considered to best characterize 'dose.' Two temporal patterns of exposure (duration vs. repetition) were used to characterize 'dosage.' The roles of long-term exposure vs. unaccustomed work were mentioned, but not incorporated into the models. RESULTS Compressive force transmitted to the extensor retinaculum was considered the critical factor in the model for tendon entrapment at the dorsal wrist compartments. Two models were proposed for lateral epicondylitis. One emphasized the role of eccentric exertions; the other emphasized contact pressure from the radial head. The model for peritendinitis relied on localized muscle fatigue. Seven plausible models were presented for carpal tunnel syndrome. CONCLUSIONS It is possible to propose biologically plausible models of pathogenesis that are both coherent with current knowledge of tissue responses and consistent with clinical observations; however, more than one model was plausible for some conditions. Additional research is needed to determine which, if any, of the proposed models might be correct. Such models may be useful to health care providers and ergonomists in the context of primary, secondary, or tertiary prevention.
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Affiliation(s)
- J Steven Moore
- Department of Environmental and Occupational Health, School of Rural Public Health, Texas A&M University Health Science Center, Bryan 77802, USA.
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Covizi DZ, Felisbino SL, Gomes L, Pimentel ER, Carvalho HF. Regional adaptations in three rat tendons. Tissue Cell 2001; 33:483-90. [PMID: 11949784 DOI: 10.1054/tice.2001.0202] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Although detailed histological and immunocytochemical studies have been published for the rat calcanear tendon (CT), little is known of the structure, composition and biomechanics of the deep (DFT) and superficial (SFT) flexor tendons. In this study, we examined the structural specialization of these three tendons in 90-day-old rats by applying histochemical and biochemical assays to different tendon regions (proximal, intermediate and distal regions of the DFT and SFT, and proximal and distal regions of the CT). There were regional differences in tissue structure, glycosaminoglycan type and content, swelling properties and in the amount and distribution of elastic fibers. Dermatan sulfate occurred in all regions, but chondroitin sulfate predominated in the intermediate region of the DFT and in the distal region of the CT. These two chondroitin sulfate-bearing regions showed swelling in water, while all other regions lost fluid in water. Fibrocartilaginous sites were observed on the CT, one at the insertion to the bone and another distally at the innermost area of the tendon. The intermediate region of the DFT showed round cells disposed in lacunae, while the proximal and distal regions were typically fibrous. The intermediate region of the SFT showed a wavy array of collagen bundles but neither toluidine blue staining in the matrix nor round cells. Elastic fibers were present in each region of the three tendons, but were more prominent in the intermediate zone of the SFT. These results demonstrate regional variation in the three tendons. Tendon differentiation may occur by an increase in the number of elastic fibers and by variations in the arrangement of collagen fibers, without fibrocartilage formation.
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Affiliation(s)
- D Z Covizi
- Department of Cell Biology, Institute of Biology, State University of Campinas (UNICAMP), SP, Brazil
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Abstract
Tendon regions subjected almost exclusively to tension differ from regions subjected to high levels of compression as well as tension. Regions not exposed to compression consist primarily of spindle-shaped fibroblasts surrounded by densely packed longitudinally oriented collagen fibrils formed principally from type-I collagen. In contrast, regions subjected to compression have a fibrocartilagenous structure and composition: they consist of spherical cells surrounded by a matrix containing hyaline cartilage proteoglycans (aggrecan) and type-II collagen as well as type-I collagen. Reducing their adhesion to the matrix may help cells in the latter regions establish and maintain a spherical shape and minimize their deformation when the tissue is subjected to mechanical stress. We hypothesized that expression of tenascin-C, an anti-adhesive protein, is part of the adaptation of tendon cells to compression that helps establish and maintain fibrocartilagenous regions. To test this hypothesis, we compared segments of bovine flexor tendons subjected to repetitive compression (distal) with segments that are not subjected to compression (proximal) to determine whether they differed in tenascin-C content and expression. RNA and protein analyses showed that tenascin-C expression was elevated in the distal tendon. Tendon cells from the distal segment expressed more tenascin-C mRNA than did cells from the proximal segments for as long as 4 days in cell culture, indicating that increased tenascin-C expression is a relatively stable feature of the distal cells. Moreover, purified tenascin-C inhibited the attachment of cultured tendon cells to fibronectin. These observations support the hypothesis that tenascin-C expression is a cellular adaptation to compression that helps establish and maintain fibrocartilagenous regions of tendons by decreasing cell-matrix adhesion.
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Affiliation(s)
- D Mehr
- Iowa City Veterans Administration Medical Center and Department of Orthopaedics, University of Iowa, USA
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Abstract
Flexor tendon entrapment of the digits is a disorder characterized by snapping or locking of the thumb or fingers (with or without pain). Most cases are secondary to thickening of the digit's A1 pulley, but other pathogeneses include tendon abnormalities at the level of the carpal tunnel, thickening of other pulleys, and abnormalities of the metacarpal-phalangeal joint. Its historical name, stenosing tenosynovitis of the digits, is inappropriate because histological studies document a lack of inflammation. Flexor tendon entrapment of the digits is a relatively common, uncomplicated, and non-controversial musculotendinous disorder of the distal upper extremity. The purpose of this invited review is to summarize information from the medical literature on aspects of this condition likely to be of interest and relevant to occupational medicine practitioners. Topics covered include normal anatomy and kinesiology, history, clinical observations related to diagnosis, pathology, pathophysiology, clinical observations on etiology, descriptive epidemiology, epidemiological studies, and case management. Models for the pathogenesis of flexor tendon entrapment of the digits are proposed, and opportunities for future research are presented.
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Affiliation(s)
- J S Moore
- NSF Industry/University Cooperative Research Center in Ergonomics, Texas A&M University, College Station 78443-3133, USA.
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Reinboth BJ, Finnis ML, Gibson MA, Sandberg LB, Cleary EG. Developmental expression of dermatan sulfate proteoglycans in the elastic bovine nuchal ligament. Matrix Biol 2000; 19:149-62. [PMID: 10842098 DOI: 10.1016/s0945-053x(00)00060-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The nuchal ligament of bovines is a useful system in which to study elastic fibre formation since it contains up to 83% elastin and undergoes a period of rapid elastinogenesis during the last trimester of fetal development and in the first four post-natal months. To identify proteoglycans (PGs) which may be involved in this process we initially investigated changes in the glycosaminoglycan (GAG) profiles during nuchal ligament development. In contrast to the collagenous Achilles tendon, nuchal ligament exhibited: (a) elevated hyaluronan (HA) levels in the peak period of elastin-associated microfibril (fibrillin) synthesis (130-200 days) which precedes elastinogenesis; and (b) markedly increased synthesis of a glucuronate-rich copolymeric form of dermatan sulfate (DS) in the period corresponding to elastin formation (200-270 days). Analysis of DSPGs isolated from 230-day nuchal ligament showed that this copolymer was predominantly associated with a glycoform of biglycan which was specifically elevated at this stage in development. This finding was consistent with Northern blot analysis which showed that steady-state biglycan mRNA levels increased significantly during the elastinogenic period. In contrast, the mRNA levels for decorin, the only other DSPG detected in this tissue, declined rapidly after 140 days of fetal development. In conclusion, the results suggest that HA may play a role in microfibril assembly and that a specific glycoform of biglycan may be associated with the elastinogenic phase of elastic fibre formation.
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Affiliation(s)
- B J Reinboth
- Department of Pathology, University of Adelaide, South Australia
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