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Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice.

Nat Commun. 2018; 
Wang X, Li F, Xie L, Crane J, Zhen G, Mishina Y, Deng R, Gao B, Chen H, Liu S,, Yang P, Gao M, Tu M, Wang Y, Wan M, Fan C, Cao X.
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摘要

Acquired heterotopic ossification (HO) is a painful and debilitating disease characterized by extraskeletal bone formation after injury. The exact pathogenesis of HO remains unknown. Here we show that TGF-β initiates and promotes HO in mice. We find that calcified cartilage and newly formed bone resorb osteoclasts after onset of HO, which leads to high levels of active TGF-β that recruit mesenchymal stromal/progenitor cells (MSPCs) in the HO microenvironment. Transgenic expression of active TGF-β in tendon induces spontaneous HO, whereas systemic injection of a TGF-β neutralizing antibody attenuates ectopic bone formation in traumatic and BMP-induced mouse HO models, and in a fibrodysplasia ossificans progr... More

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