title: Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle.
abstract: 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-beta1 (TGF-beta1) 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-beta1, 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-beta1, 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.
authors.affiliation: Institute of Sports Medicine, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark. katjaheinemeier@hotmail.com
authors.forename: K M
authors.initials: KM
authors.lastname: Heinemeier
authors.forename: J L
authors.initials: JL
authors.lastname: Olesen
authors.forename: F
authors.initials: F
authors.lastname: Haddad
authors.forename: P
authors.initials: P
authors.lastname: Schjerling
authors.forename: K M
authors.initials: KM
authors.lastname: Baldwin
authors.forename: M
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000125:Achilles Tendon / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005260:Female; D019417:Hindlimb Suspension; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D016474:Weight-Bearing
chemical_list: C526316:CCN2 protein, rat; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D036341:Intercellular Signaling Peptides and Proteins; C525913:Mstn protein, rat; D055435:Myostatin; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D007334:Insulin-Like Growth Factor I; D003094:Collagen