脯氨酰羟化酶 2 抑制剂 cpd17 对小鼠成骨前体细胞的影响.

BACKGROUND: Prolyl hydroxylase domain 2 (PHD2) inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats. cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University. It is effective in the treatment of renal anemia with few side effects, but its effect on bone formation and bone resorption is still unclear. OBJECTIVE: To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS: Osteogenic precursor cells were treated with cpd17. Alkaline phosphatase activity and extracellular matrix mineralization were measured, and the expression levels of osteogenesis- and osteoclastogenesis-related markers, as well as PHD2 and hypoxia-inducible factor 1α, were detected. After inhibition of the hypoxia-inducible factor 1α pathway using LW6 (a hypoxia-inducible factor 1α pathway inhibitor), alkaline phosphatase activity and extracellular matrix mineralization were detected again, as well as the expression levels of osteogenesis- and osteoclastogenesis-related markers, PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION: cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization, up-regulated the expression of osteogenesis-related markers, down-regulated the expression of osteoclastogenesis-related markers, up-regulated the expression of hypoxia-inducible factor 1α, down-regulate the expression of PHD2. However, cpd17’s effects were significantly attenuated by LW6. To conclude, the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway. [ABSTRACT FROM AUTHOR]