Abstract
BackgroundExpression of the growth factor osteoactivin (OA) increases during tissue degeneration and regeneration, fracture repair and after denervation-induced disuse atrophy, concomitant with increased matrix metalloproteinases (MMPs). However, OA’s expression with repetitive overuse injuries is unknown. The aim of this study was to evaluate: 1) OA expression in an operant rat model of repetitive overuse; 2) expression of MMPs; 3) inflammatory cytokines indicative of injury or inflammation; and 4) the inducible form of heat shock protein 70 (HSPA1A/HSP72) as the latter is known to increase during metabolic stress and to be involved in cellular repair. Young adult female rats performed a high repetition negligible force (HRNF) food retrieval task for up to 6 weeks and were compared to control rats.MethodsFlexor digitorum muscles and tendons were collected from 22 young adult female rats performing a HRNF reaching task for 3 to 6 weeks, and 12 food restricted control (FRC) rats. OA mRNA levels were assessed by quantitative polymerase chain reaction (qPCR). OA, MMP-1, -2, -3, and -13 and HSP72 protein expression was assayed using Western blotting. Immunohistochemistry and image analysis was used to evaluate OA and HSP72 expression. ELISA was performed for HSP72 and inflammatory cytokines.ResultsFlexor digitorum muscles and tendons from 6-week HRNF rats showed increased OA mRNA and protein expression compared to FRC rats. MMP-1, -2 and -3 progressively increased in muscles whereas MMP-1 and -3 increased in tendons with HRNF task performance. HSP72 increased in 6-week HRNF muscles and tendons, compared to controls, and co-localized with OA in the myofiber sarcolemma. IL-1alpha and beta increased transiently in tendons or muscles in HRNF week 3 before resolving in week 6.ConclusionThe simultaneous increases of OA with factors involved in tissue repair (MMPs and HSP72) supports a role of OA in tissue regeneration after repetitive overuse.
Highlights
Expression of the growth factor osteoactivin (OA) increases during tissue degeneration and regeneration, fracture repair and after denervation-induced disuse atrophy, concomitant with increased matrix metalloproteinases (MMPs)
OA was localized to the sarcolemma and to macrophage-like cells located between individual muscle fibers in 6-week high repetition negligible force (HRNF) muscles yet was absent in control muscles (Fig. 1f and g)
No increase was observed for IL-1beta in Discussion For the first time to our knowledge, we show in a rat model of limb overuse that expression of the growth factor osteoactivin (OA) increases progressively in forearm muscles and tendons with prolonged performance of an upper extremity high repetition negligible force (HRNF) task for up to 6 weeks
Summary
Expression of the growth factor osteoactivin (OA) increases during tissue degeneration and regeneration, fracture repair and after denervation-induced disuse atrophy, concomitant with increased matrix metalloproteinases (MMPs). Barbe and Barr have developed an operant rat model of upper extremity overuse in which rats learn to perform repetitive tasks, such as a high repetition negligible force (HRNF) food retrieval task In this particular task, rats reach at a rate of 4 reaches/min into a portal to retrieve a 45-mg pellet of food for 2 h/day (in four 30 min sessions/day) for 3 days/week. Rats reach at a rate of 4 reaches/min into a portal to retrieve a 45-mg pellet of food for 2 h/day (in four 30 min sessions/day) for 3 days/week Performance of this HRNF task leads to modest signs of myositis and tendinitis in forearm muscles and tendons and increased focal sites of myotendon fray and fibroblast proliferation [9, 10]. It is known that inflammatory cells infiltrate tissues, which, along with injured cells, produce inflammatory cytokines and other mediators that either exacerbate damage or assist in tissue repair [11, 12]
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