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This Article Full Text Full Text (PDF) All Versions of this Article: 106/1/178    most recent 91092.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Heinemeier, K. M. Articles by Kjaer, M. Search for Related Content PubMed PubMed Citation Articles by Heinemeier, K. M. Articles by Kjaer, M.

Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle

¹Institute of Sports Medicine, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen; ²Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark; and ³Department of Physiology and Biophysics, University of California, Irvine, California; ⁴Department of Molecular Muscle Biology, Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen; and ⁵Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Submitted 12 August 2008 ; accepted in final form 31 October 2008

Tendon tissue and the extracellular matrix of skeletal muscle respond to mechanical loading by increased collagen expression and synthesis. This response is likely a secondary effect of a mechanically induced expression of growth factors, including transforming growth factor-β1 (TGF-β1) and insulin-like growth factor-I (IGF-I). It is not known whether unloading of tendon tissue can reduce the expression of collagen and collagen-inducing growth factors. Furthermore, the coordinated response of tendon and muscle tissue to disuse, followed by reloading, is unclear. Female Sprague-Dawley rats were subjected to hindlimb suspension (HS) for 7 or 14 days, followed by 2, 4, 8, or 16 days of reload (RL) (n = 8 in each group). Age-matched controls were included for day 0, day 14 HS, and day 16 RL (n = 8). mRNA expression levels for collagen I (COL1A1), collagen III (COL3A1), TGF-β1, connective tissue growth factor (CTGF), myostatin, and IGF-I isoforms were measured by real-time RT-PCR in Achilles tendon and soleus muscle. The tendon mass was unchanged, while the muscle mass was reduced by 50% after HS (P < 0.05) and returned to control levels during RL. Collagen I and III, TGF-β1, and CTGF mRNA levels were unaltered by HS, although collagen III tended to decrease in muscle at day 7 HS. IGF-I isoforms were significantly induced in tendon after 7 days of HS (P < 0.001), and mechanogrowth factor increased in muscle at day 14 HS (P < 0.05). Reload increased muscle collagen I and III mRNA (>10-fold) (P < 0.001) and growth factor expression (P < 0.05), while the tendon response was limited to a moderate induction of collagen expression (2-fold) (P < 0.05). Unloading of tendon and muscle tissue did not reduce expression of collagen and collagen-inducing growth factors, indicating that the response to unloading is not opposite that of loading. Furthermore, the tendon response was clearly different and less pronounced than the muscle tissue response.

extracellular matrix-related genes; skeletal muscle; hindlimb suspension