Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts
Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts
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DOI：
10.1172/jci29463
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发表时间：
2006-12-01
影响因子：
15.9
通讯作者：
Carmeliet, Geert
中科院分区：
文献类型：
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作者：
Masuyama, Ritsuko;Stockmans, Ingrid;Carmeliet, Geert
由1 α 25-二羟维生素D-3 [1，25（OH）（2）D-3]诱导的基因组作用对正常骨代谢至关重要，主要是因为它们调节活性肠钙转运。为了评估维生素D受体（VDR）是否在生长板发育和软骨内骨形成中具有特定作用，我们研究了软骨细胞中VDR条件性失活的小鼠。生长板软骨细胞发育不受VDR缺乏的影响。然而，幼年小鼠的血管侵袭受损，破骨细胞数量减少，导致骨小梁质量增加。体外实验证实，软骨细胞中的VDR信号通过诱导NF-κ B配体受体激活因子（RANKL）表达直接调节破骨细胞生成。值得注意的是，软骨细胞特异性VDR缺失小鼠的矿物质稳态也受到影响，因为年轻小鼠的血清磷酸盐和1，25（OH）（2）D水平增加，而生长板活动对年轻小鼠很重要。体内和体外分析均表明，软骨细胞中的VDR失活降低了成骨细胞对FGF 23的表达，并因此导致Ia.羟化酶和IIa型磷酸钠协同转运蛋白。综上所述，我们的研究结果提供了证据表明，软骨细胞中的VDR信号是骨发育过程中破骨细胞及时形成所必需的，也是磷酸盐稳态中骨的内分泌作用所必需的。
Genomic actions induced by 1 alpha 25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] are crucial for normal bone metabolism, mainly because they regulate active intestinal calcium transport. To evaluate whether the vitamin D receptor (VDR) has a specific role in growth-plate development and endochondral bone formation, we investigated mice with conditional inactivation of VDR in chondrocytes. Growth-plate chondrocyte development was not affected by the lack of VDR. Yet vascular invasion was impaired, and osteoclast number was reduced in juvenile mice, resulting in increased trabecular bone mass. In vitro experiments confirmed that VDR signaling in chondrocytes directly regulated osteoclastogenesis by inducing receptor activator of NF-kappa B ligand (RANKL) expression. Remarkably, mineral homeostasis was also affected in chondrocyte-specific VDR-null mice, as serum phosphate and 1,25(OH)(2)D levels were increased in young mice, in whom growth-plate activity is important. Both in vivo and in vitro analysis indicated that VDR inactivation in chondrocytes reduced the expression of FGF23 by osteoblasts and consequently led to increased renal expression of la.-hydroxylase and of sodium phosphate cotransporter type IIa. Taken together, our findings provide evidence that VDR signaling in chondrocytes is required for timely osteoclast formation during bone development and for the endocrine action of bone in phosphate homeostasis.