Gap Junctions Regulate Responses of Tendon Cells Ex Vivo to Mechanical Loading

Banes, Albert J.; Weinhold, Paul S.; Yang, Xi; Tsuzaki, Mari; Bynum, Donald K.; Bottlang, Michael; Brown, Tom

doi:10.1097/00003086-199910001-00034

Cited by 104 publications

(89 citation statements)

References 53 publications

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“…Tenocytes appear to share elements of a load-sensing mechanism similar to osteoblasts and osteocytes; stretch-activated potassium and calcium channels, internal calcium release, interstitial ATP release, and gap junction signaling all play a role in the proliferative response to membrane deformation, substrate deformation, or fluid shear (43)(44)(45)(46)(47). In elongated tenocytes, proliferation and collagen synthesis in response to ex vivo loading of chicken flexor tendon could be blocked by a gap junction inhibitor (48). The current study highlights the need to examine cellcell and cell-matrix interactions in the early stages of tendinosis (e.g., tenocyte expression and activation of integrins, cadherins, and connexins).…”

Section: Discussionmentioning

confidence: 99%

Tenocyte responses to mechanical loading in vivo: A role for local insulin‐like growth factor 1 signaling in early tendinosis in rats

Scott

Cook

Hart

et al. 2007

Arthritis & Rheumatism

146

138

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Objective. To investigate tenocyte regulatory events during the development of overuse supraspinatus tendinosis in rats.Methods. Supraspinatus tendinosis was induced by running rats downhill at 1 km/hour for 1 hour a day. Tendons were harvested at 4, 8, 12, and 16 weeks and processed for brightfield, polarized light, or transmission electron microscopy. The development of tendinosis was assessed semiquantitatively using a modified Bonar histopathologic scale. Apoptosis and proliferation were examined using antibodies against fragmented DNA or proliferating cell nuclear antigen, respectively. Insulin-like growth factor 1 (IGF-1) expression was determined by computer-assisted quantification of immunohistochemical reaction. Local IGF-1 signaling was probed using antibodies to phosphorylated insulin receptor substrate 1 (IRS-1) and ERK-1/2.Results. Tendinosis was present after 12 weeks of downhill running and was characterized by tenocyte rounding and proliferation as well as by glycosaminoglycan accumulation and collagen fragmentation. The proliferation index was elevated in CD90؉ tenocytes in association with tendinosis and correlated with increased local IGF-1 expression by tenocytes and phosphorylation of IRS-1 and ERK-1/2. Both apoptosis and cellular inflammation were absent at all time points. Conclusion. In this animal model, early tendinosis was associated with local stimulation of tenocytes rather than with extrinsic inflammation or apoptosis. Our data suggest a role for IGF-1 in the load-induced tenocyte responses during the pathogenesis of overuse tendon disorders.

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Section: Discussionmentioning

confidence: 99%

Tenocyte responses to mechanical loading in vivo: A role for local insulin‐like growth factor 1 signaling in early tendinosis in rats

Scott

Cook

Hart

et al. 2007

Arthritis & Rheumatism

146

138

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“…Convincing support from models of partial tissue dissection, where loads are shunted to intact tissue, show resulting anabolic net synthesis of functional collagen matrix, probably in direct response to increased mechanical stresses and strains in the tissue [43,69,137]. Additionally, mechanical loading has been observed to upregulate collagen synthesis of tendon fascicles [142] and whole tendons [143]. Although net collagen synthesis is generally viewed as a positive sign of functional healing, how these collagens are structured is also important (highly aligned vs. more randomly distributed).…”

Section: The Fundamental Role Of Mechanical Forces In Regulating Tendmentioning

confidence: 92%

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

2017

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“…The system would preserve the three-dimensional structure and composition of the ACL during the application of loads, thereby providing a cellular microenvironment which is similar to that in vivo. Although explant cultures have been used to study the effects of mechanical stimuli on a variety of tissues including lung parenchyma [ 161, cartilage (reviewed in [15]), tendon [6], and bone [31], we know of no previous ex vivo studies on the biological response of ligaments to mechanical loading.…”

Section: Introductionmentioning

confidence: 99%

Biomechanical regulation of type I collagen gene expression in ACLs in organ culture

Hsieh

Sah

Sung

2002

Journal Orthopaedic Research

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In this study, an ex vivo organ culture system that allows the application of controlled loads to the anterior cruciate ligament (ACL) was designed and used to characterize the influence of a step input in mechanical load on gene expression. A procedure for isolating bone-ACL-bone (B-ACL-B) complexes from rat knees was developed. After harvest and 24 hour culture, B-ACL-B complexes exhibited percentages of viability similar to that in intact ACLs (-9O'X)). Application or a physiologically relevant load of 5 N (superimposed on a 1 N tare load) resulted in changes in levels of mRNA encoding type 1 collagen. While levels of type I collagen mRNA significantly increased 32 * 13%) (mean i standard errors of the mean (SEM)) over controls within the first hour of loading, levels decreased significantly to 44 f 9% of control after 2 h. Displacements induced by the 5 N load were measured by video dimensional analysis. Calculated axial strains of 0.141 5 0.034 were achieved rapidly during the first hour and remained essentially unchanged thereafter. These results demonstrate the feasibility of maintaining ligaments in organ culture and illustrate the time course expression of type I collagen following the application of a mechanical load.

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Gap Junctions Regulate Responses of Tendon Cells Ex Vivo to Mechanical Loading

Cited by 104 publications

References 53 publications

Tenocyte responses to mechanical loading in vivo: A role for local insulin‐like growth factor 1 signaling in early tendinosis in rats

Tenocyte responses to mechanical loading in vivo: A role for local insulin‐like growth factor 1 signaling in early tendinosis in rats

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

Biomechanical regulation of type I collagen gene expression in ACLs in organ culture

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