Muscle injury promotes heterotopic ossification by stimulating local bone morphogenetic protein-7 production

肌肉损伤通过刺激局部骨形态发生蛋白-7的产生促进异位骨化

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作者:La Li, Yangzi Jiang, Hang Lin, He Shen, Jihee Sohn, Peter G Alexander, Rocky S Tuan

Background

Heterotopic ossification (HO) is a pathological condition of abnormal bone formation in soft tissue, which causes pain and restricted range of motion in patients. There are two broad categories of HO, hereditary and acquired. Although different types of HO do not use identical mechanistic pathways of pathogenesis, muscle injury appears to be a unifying feature for all types of HO. However, little is known about the mechanisms by which muscle injury facilitates HO formation.

Conclusion

In summary, our study has identified BMP-7 as a key osteoinductive factor in injured muscle that facilitates HO formation. The translational potential of this article: Our results provide a candidate mechanistic rationale for the use of antiinflammatory drugs in the prevention of HO.

Results

We found that muscle injury augmented HO formation and that this effect was correlated with BMP signalling activation and upregulation of BMP-7 expression at the early phase of HO progression. We further demonstrated that inhibition of BMP-7 activity in vitro suppressed the osteogenesis-promoting effect of conditioned medium derived from injured muscle tissue and in vivo reduced the volume of HO formation. We also showed that antiinflammatory drug treatment reduced the volume of HO with concomitant reduction in BMP-7 production.

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