Fig. 7

Inhibition of HDAC1 reverses the TGF-β1 suppression on osteogenesisin vitroand rescues the osteoporotic phenotypein vivo. A - C In vitro osteogenesis. C3H10T1/2 cells with knockdown of Hdac1 (A), Atf3 or Tgif1 (B), or with HDAC inhibitor supplements (C) were treated with TGF-β1 (1 nM) and/or BMP4 (3 nM) during osteoblastogenic induction. The ALP activity was revealed by representative staining images or by intensity quantification. n = 3 independent experiments. D and E In vivo chronic osteoporosis model. Mice undergoing ovariectomy (OVX)-induced osteoporosis were used for bone marrow isolation or subsequent purification of BM-MSCs. Bone marrows (D) or the derived BM-MSCs treated with TGF-β1 (1 nM) for 30 min (E) were subjected to Western blotting to detect the indicated factors. (F - H)In vivo acute bone loss model. Mice undergoing sRANKL-induced bone loss were further injected without or with different HDAC inhibitors as indicated. Bone marrows (F) were isolated and then subjected to Western blotting to detect the indicated factors. Distal femurs from mice were subjected to µCT analysis. Representative images (G) and derived bone parameters (H), including BV/TV, Tb.Sp, Tb.Th, Tb.N and bone mineral density (BMD), were shown and compared. ‘C’ denotes the vehicle control for drugs. Data are means ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, compared to indicated sample. One-way ANOVA followed by multiple comparison test