Knockout of TRPV6 Causes Osteopenia in Mice by Increasing Osteoclastic Differentiation and Activity
Knockout of TRPV6 Causes Osteopenia in Mice by Increasing Osteoclastic Differentiation and Activity
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DOI：
10.1159/000358653
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Chen, Aimin
中科院分区：
文献类型：
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作者：
Chen, Fangjing;Ni, Bin;Chen, Aimin
背景：破骨细胞分化需要钙离子（Ca2+）信号。先前的研究表明，瞬时受体电位香草样蛋白5 （TRPV5）是破骨细胞发生和骨吸收中必需的Ca2+转运蛋白。TRPV5和TRPV6是瞬时受体电位（TRP）超家族中两个高度同源的成员。然而，TRPV6在骨代谢中的作用仍然存在争议，TRPV6在核因子k（-B）配体受体激活物（RANKL）诱导的破骨细胞发生中的作用尚不清楚。方法：采用基因敲除小鼠、RNA干扰、western blot、实时荧光定量PCR、抗酒石酸酸性磷酸酶（TRAP）染色、窝形法、组织形态学和血清参数测定等方法，研究TRPV6在骨稳态、破骨细胞生成和骨吸收中的作用。结果：我们发现TRPV6缺失导致TRPV6敲除小鼠（TRPV6(-/-)）骨微结构明显破坏，表明TRPV6是骨稳态的关键调节因子。Trpv6的失活对成骨细胞骨的形成没有影响。然而，TRAP染色定量显示，TRPV6（-/-）小鼠股骨骨切片的干骺端破骨细胞数量和表面积显著增加。与我们在TRPV6（-/-）小鼠中观察到的结果一致，体外TRPV6缺失显著增加了破骨细胞分化和骨吸收活性。结论：基于以上结果，我们可以得出TRPV6在骨代谢中起重要作用，是破骨细胞分化和骨吸收的关键调节因子。版权所有(c) 2014 S. Karger AG，巴塞尔
Background: Calcium ion (Ca2+) signals are required for osteoclast differentiation. Previous study showed that transient receptor potential vanilloid 5 (TRPV5) is an essential Ca2+ transporter in osteoclastogenesis and bone resorption. TRPV5 and TRPV6 represent two highly homologous members within the transient receptor potential (TRP) superfamily. However, the role of TRPV6 in bone metabolism is still controversial and little is known about the involvement of TRPV6 in receptor activator of nuclear factor k(-B) ligand (RANKL)-induced osteoclastogenesis. Methods: In our study, gene knockout mice, RNA interference, western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, histomorphometry and measurement of serum parameters were employed to investigate the role of TRPV6 in bone homeostasis, osteoclastogenesis and bone resorption. Results: We found that TRPV6 depletion results in noticeable destruction of bone microarchitecture in TRPV6 knockout mice (TRPV6(-/-)), suggesting that TRPV6 is a critical regulator in bone homeostasis. Inactivation of Trpv6 had no effect on osteoblastic bone formation. However, quantification of the TRAP staining showed a significantly increased osteoclast number and surface area in the metaphyseal area of femurs bone sections derived from TRPV6(-/-) mice. In agreement with our observations from TRPV6(-/-) mice, TRPV6 depletion in vitro significantly increased osteoclasts differentiation and bone resorption activity. Conclusion: Based on these results above, we can draw conclusions that TRPV6 plays an essential role in bone metabolism and is a critical regulator in osteoclasts differentiation and bone resorption. Copyright (c) 2014 S. Karger AG, Basel