| First Author | Wang X | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 551 |
| PubMed ID | 29416028 | Mgi Jnum | J:257692 |
| Mgi Id | MGI:6119070 | Doi | 10.1038/s41467-018-02988-5 |
| Citation | Wang X, et al. (2018) Inhibition of overactive TGF-beta attenuates progression of heterotopic ossification in mice. Nat Commun 9(1):551 |
| abstractText | 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-beta 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-beta that recruit mesenchymal stromal/progenitor cells (MSPCs) in the HO microenvironment. Transgenic expression of active TGF-beta in tendon induces spontaneous HO, whereas systemic injection of a TGF-beta neutralizing antibody attenuates ectopic bone formation in traumatic and BMP-induced mouse HO models, and in a fibrodysplasia ossificans progressive mouse model. Moreover, inducible knockout of the TGF-beta type II receptor in MSPCs inhibits HO progression in HO mouse models. Our study points toward elevated levels of active TGF-beta as inducers and promoters of ectopic bone formation, and suggest that TGF-beta might be a therapeutic target in HO. |
