The calcium channel TRPV6 is a novel regulator of RANKL-induced osteoclastic differentiation and bone absorption activity through the IGF-PI3K-AKT pathway.
The calcium channel TRPV6 is a novel regulator of RANKL-induced osteoclastic differentiation and bone absorption activity through the IGF-PI3K-AKT pathway.
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钙通道 TRPV6 是通过 IGF-PI3K-AKT 途径调节 RANKL 诱导的破骨细胞分化和骨吸收活性的新型调节剂
DOI：
10.1111/cpr.12955
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发表时间：
2021-01
影响因子：
8.5
通讯作者：
Ye TW
中科院分区：
文献类型：
--
作者：
Ma J;Zhu L;Zhou Z;Song T;Yang L;Yan X;Chen A;Ye TW
钙离子信号在破骨细胞分化中起重要作用。瞬时受体电位香草酸6（TRPV 6）是骨稳态的调节剂。然而，目前还不清楚TRPV 6是否参与破骨细胞的形成。因此，本研究的目的是评估TPRV 6在骨代谢中的作用，并阐明其在细胞水平上对破骨细胞的调节作用。使用微型计算机断层扫描和组织学分析检查Trpv 6敲除小鼠的骨结构和组织学变化。为了研究Trpv 6对破骨细胞功能的影响，我们通过慢病毒转染分别在破骨细胞中沉默或过表达Trpv 6。通过抗酒石酸酸性磷酸酶（TRAP）染色和窝形成试验测定破骨细胞分化和骨吸收活力。通过qRT-PCR测量破骨细胞标志物基因的表达，包括组织蛋白酶k、DC-STAMP、Atp 6v 0 d2和TRAP。采用细胞免疫荧光和Western blotting方法探讨IGF-PI 3 K-AKT通路参与Trpv 6调控破骨细胞形成和骨吸收的机制。我们发现Trpv 6基因敲除可诱导小鼠骨质疏松并增强骨吸收，但不影响骨形成。进一步的研究表明Trpv 6主要分布在破骨细胞的细胞膜上，对破骨细胞的分化和功能起负调节作用。在机制上，Trpv 6通过降低IGF-PI 3 K-AKT信号通路中磷蛋白/总蛋白的比率来抑制破骨细胞生成。阻断IGF-PI 3 K-AKT通路可显著减轻Trpv 6对破骨细胞形成的抑制作用。我们的研究证实了Trpv 6在骨代谢中的重要作用，并阐明了其在破骨细胞水平上的调节作用。总而言之，这项研究可能会启发治疗骨质疏松症的新策略。瞬时受体电位香草酸6（TRPV 6）是RANKL诱导的破骨细胞分化和骨吸收活性的关键负调节因子。TRPV 6通过抑制IGF/PI 3 K/AKT信号通路负调节破骨细胞形成和骨吸收。
Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a regulator of bone homeostasis. However, it was unclear whether TRPV6 was involved in osteoclast formation. Therefore, the aim of this study was to evaluate the role of TPRV6 in bone metabolism and to clarify its regulatory role in osteoclasts at the cellular level. Bone structure and histological changes in Trpv6 knockout mice were examined using micro‐computed tomography and histological analyses. To investigate the effects of Trpv6 on osteoclast function, we silenced or overexpressed Trpv6 in osteoclasts via lentivirus transfection, respectively. Osteoclast differentiation and bone resorption viability were measured by tartrate‐resistant acid phosphatase (TRAP) staining and pit formation assays. The expression of osteoclast marker genes, including cathepsin k, DC‐STAMP, Atp6v0d2 and TRAP, was measured by qRT‐PCR. Cell immunofluorescence and Western blotting were applied to explore the mechanisms by which the IGF‐PI3K‐AKT pathway was involved in the regulation of osteoclast formation and bone resorption by Trpv6. We found that knockout of Trpv6 induced osteoporosis and enhanced bone resorption in mice, but did not affect bone formation. Further studies showed that Trpv6, which was distributed on the cell membrane of osteoclasts, acted as a negative regulator for osteoclast differentiation and function. Mechanistically, Trpv6 suppressed osteoclastogenesis by decreasing the ratios of phosphoprotein/total protein in the IGF–PI3K–AKT signalling pathway. Blocking of the IGF–PI3K–AKT pathway significantly alleviated the inhibitory effect of Trpv6 on osteoclasts formation. Our study confirmed the important role of Trpv6 in bone metabolism and clarified its regulatory role in osteoclasts at the cellular level. Taken together, this study may inspire a new strategy for the treatment of osteoporosis. The transient receptor potential vanilloid 6 (TRPV6) was a critical negative regulator in RANKL‐induced osteoclast differentiation and bone resorption activity. TRPV6 negatively regulates osteoclast formation and bone resorption by inhibiting the IGF/PI3K/AKT signalling pathway.
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影响因子：
4.1
作者：
Lieben, L.;Benn, B. S.;Ajibade, D.;Stockmans, I.;Moermans, K.;Hediger, M. A.;Peng, J. B.;Christakos, S.;Bouillon, R.;Carmeliet, G.
通讯作者：
Carmeliet, G.
影响因子：
4.8
作者：
Kim, Min Seuk;Yang, Yu-Mi;Shin, Dong Min
通讯作者：
Shin, Dong Min
影响因子：
6.2
作者：
DeMambro, Victoria E.;Maile, Laura;Wai, Christine;Kawai, Masanobu;Cascella, Teresa;Rosen, Clifford J.;Clemmons, David
通讯作者：
Clemmons, David
影响因子：
--
作者：
Chen, Fangjing;Ni, Bin;Chen, Aimin
通讯作者：
Chen, Aimin
影响因子：
4.8
作者：
Hasegawa, Hiroya;Kido, Seisui;Tomomura, Akito
通讯作者：
Tomomura, Akito