Fig. 7
From: Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice
Inducible knockout of Tgfbr2 in Nestin+ cells attenuates HO formation in ATP and BGI mice. a, c Micro CT images and b, d quantifications of a, b Achilles tendons or c, d hamstring muscles of Nestin-creERT2::Tgfbr2flox/flox mice 2 months treated with vehicle or tamoxifen after undergoing ATP or BGI surgery, respectively. Scale bar, 2 mm. e, f SOFG staining of e Achilles tendons or f hamstring muscles of Tgfbr2flox/flox and Tgfbr2−/− mice 2 months after ATP or BGI, respectively. Scale bar, 50 μm g, i Nestin+ (red) cells in the ectopic bone marrow and h, j quantifications of Tgfbr2flox/flox and Tgfbr2−/− mice after ATP or BGI, respectively. Scale bar, 50 μm. Blue indicates DAPI staining of nuclei. k, m CD31+ (red) and Emcn+ (green) cells in the ectopic bone marrow and quantifications of Tgfbr2flox/flox and Tgfbr2−/− mice after ATP or BGI. Scale bars, 100 μm. Yellow indicates type H vessels. a–n n = 8 per group. All data are shown as the mean ± s.d. *p < 0.05 as determined by two-tailed, unpaired Student’s t-test. o Hypothetical diagram of HO formation. After HO induction, abundant immune cells are infiltrated in the injury sites and produce TGF-β. Next, the chondrocytes proliferate and undergo hypertrophy and calcification. Finally, osteoclasts resorb calcified cartilage and free TGF-β from latent protein and diffuse to the ectopic bone marrow cavity. Active TGF-β recruits MSPCs to form type H vessels and for osteoblastic differentiation
