Healing Effects Of Application Of Myostatin Inhibitors At Different Stages On Fractures In Mice

BACKGROUND: Myostatin (GDF-8), a member of the transforming growth factor-beta(TGF-β) superfamily of secreted growth and differentiation factors, is a negative regulator ofskeletal muscle growth。It is highly expressed in skeletalmuscle, and myostatin loss-of- functionleads to doubling of skeletal muscle mass. Myostatin-deficient mice have been used as a modelfor studying muscle-bone interactions. Recent researches have found that myostatin knockoutmice showed a significant increase in muscle mass; the intensity and mineralization of the wholeskeleton increase as well. Myostatin expression is found in the early stage of fracture repair.PURPOSE: To explore the effects of application of myostatin at different stages on the callusamount and bone mineral density of fibula fractures in mice.METHODS: Fibula fracture model was constructed in mice. The 48 model mice were randomlydivided into three groups: control group (empty treatment other than model construction), 0 daygroup, 1 week group and 2 weeks group (mice in the la tter three groups were injected withmyostatin antibody of the same dose at different starting times after model construction). Thecallus amount of the fractures was measured in the 4thweek after model construction. Myostatincontent changes and muscle tissue changes were observed.RESULTS AND CONCLUSION: The success rate of model construction was 80%. There was nosignificant difference in mouse body mass among groups (P > 0.05). The mass of gastrocnemius and the bonemineral density of the callus in the 0 day group were significantly higher than that in the other three groups (P< 0.01); there was no significant difference between the other three groups. Compared with the other groups,the tissue morphology of the myostatin content in the 0 day group also had an intuitive difference. Thesefindings indicate that the early application of myostatin inhibitors after model construction can increase thebone mineral density and promote muscle proliferation in mouse fractures.