Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro
Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro
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DOI：
10.1359/jbmr.080220
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发表时间：
2008-06-01
影响因子：
6.2
通讯作者：
Maeda, Norihiko
中科院分区：
文献类型：
--
作者：
Wang, Hua;Yoshiko, Yuji;Maeda, Norihiko
简介：成纤维细胞生长因子 (FGF)23 主要在骨骼中产生，作为全身磷酸盐因子作用于肾脏；高水平会导致佝偻病和骨软化症。然而，目前尚不清楚FGF23是否局部直接作用于骨形成。 材料和方法：我们利用腺病毒过表达系统，在胎鼠颅骨（RC）细胞培养物的成骨细胞发育过程中以特定阶段的方式过表达人FGF23，并分析其对骨祖细胞增殖、骨样结节形成和矿化的影响。还通过壁骨器官培养物中的钙黄绿素标记来测量骨形成。最后，我们探讨了 FGF 受体 (FGFR) 酪氨酸磷酸化在矿化结节形成中的作用。结果：RC 细胞中 FGF23 的过度表达独立抑制结节形成和矿化，但不抑制骨祖细胞增殖。 FGF23 水平升高也抑制了壁骨器官培养模型中的骨形成。 FGF23 过表达增强了 FGFR 的磷酸化，而 FGF23 过表达对矿化结节形成的损害被 FGFR1 酪氨酸激酶活性抑制剂 SU5402 消除。 结论：这些研究表明，FGF23 过表达不仅抑制成骨细胞分化，而且抑制基质矿化，而与其对 Pi 稳态的全身影响无关。
Introduction: Fibroblast growth factor (FGF)23 is produced primarily in bone and acts on kidney as a systemic phosphaturic factor; high levels result in rickets and osteomalacia. However, it remains unclear whether FGF23 acts locally and directly on bone formation.Materials and Methods: We overexpressed human FGF23 in a stage-specific manner during osteoblast development in fetal rat calvaria (RC) cell cultures by using the adenoviral overexpression system and analyzed its effects on osteoprogenitor proliferation, osteoid nodule formation, and mineralization. Bone formation was also measured by calcein labeling in parietal bone organ cultures. Finally, we addressed the role of tyrosine phosphorylation of FGF receptor (FGFR) in mineralized nodule formation.Results: Nodule formation and mineralization, but not osteoprogenitor proliferation, were independently suppressed by overexpression of FGF23 in RC cells. Increased FGF23 levels also suppressed bone formation in the parietal bone organ culture model. FGF23 overexpression enhanced phosphorylation of FGFR, whereas the impairment of mineralized nodule formation by FGF23 overexpression was abrogated by SU5402, an inhibitor of FGFR1 tyrosine kinase activity.Conclusions: These studies suggest that FGF23 overexpression suppresses not only osteoblast differentiation but also matrix mineralization independently of its systemic effects on Pi homeostasis.