MFG-E8 regulates inflammation and apoptosis in tendon healing, and promotes tendon repair: A histological and biochemical evaluation.

Several studies have identified potential roles for MFG-E8 in promoting tissue repair. However, the effects of MFG-E8 on tendon repair have not yet been investigated. Therefore, we explored the role of MFG-E8 on tendon repair using a rat model of patellar tendon injury. The patellar tendons of Sprague Dawley rats (n = 24/group) received window defects and, after modeling, three groups were randomly assigned: (a) recombinant MFG-E8 (rMFG-E8) group, implantation with MFG-E8 and fibrin glue (400 ng in 10 μl); (b) fibrin group, implantation with fibrin only; and (c) control group, without any treatment. Histopathology, immunohistochemistry, and gene expression analyses were performed at 2 and 4 weeks after healing. Administration of rMFG-E8 in injury sites significantly improved tendon healing histologically at 4 weeks after injury. In addition, numbers of M1 macrophages and M1-stimulator genes, including IFNG, Il-1B, and Il-6, were reduced in the repair sites at 2 weeks by rMFG-E8 administration. In parallel, rMFG-E8 significantly increased the number of M2 macrophages and expression of anti-inflammatory IL-10 and IL-4 at 2 weeks after injury. Treatment with rMFG-E8 markedly decreased tendon cell apoptosis. Moreover, rMFG-E8 significantly enhanced the expression of genes related to tendon matrix formation at 2 weeks after injury, including Col1a1and tenascin-C. We conclude that MFG-E8 could regulate inflammatory responses and apoptotic cell accumulation in tendon repair, and promote the healing process of injured tendon tissue. Thus, exogenous application of MFG-E8 might have therapeutic potential for repair of tendon injuries.