Protocadherin-7 contributes to maintenance of bone homeostasis through regulation of osteoclast multinucleation.
Protocadherin-7 contributes to maintenance of bone homeostasis through regulation of osteoclast multinucleation.
复制标题
DOI：
10.5483/bmbrep.2020.53.9.050
复制
发表时间：
2020-09
期刊：
影响因子：
3.8
通讯作者：
Choi Y
中科院分区：
文献类型：
--
作者：
Kim H;Takegahara N;Walsh MC;Ueda J;Fujihara Y;Ikawa M;Choi Y
破骨细胞是吸收骨的造血源性细胞。它们需要维持适当的骨稳态和骨骼强度。尽管破骨细胞分化依赖于NFκB B受体激活因子配体（RANKL）刺激，但其他分子进一步促进破骨细胞成熟。在这里，我们证明，原钙粘蛋白-7（Pcdh 7）调节多核破骨细胞的形成，并有助于维持骨稳态。我们发现，Pcdh 7的表达是由RANKL刺激诱导的，并且RNAi介导的Pcdh 7敲低导致破骨细胞形成受损。我们产生了Pcdh 7缺陷小鼠，发现由于骨吸收减少而导致骨量增加，但骨形成没有任何缺陷。使用在体外培养系统，它揭示了多核破骨细胞的形成是受损的Pcdh 7缺陷的文化，而没有明显的缺陷，观察到在分化和功能的Pcdh 7缺陷的成骨细胞。总之，这些结果揭示了破骨细胞内在的作用Pcdh 7在维持骨稳态。
Osteoclasts are hematopoietic-derived cells that resorb bone. They are required to maintain proper bone homeostasis and skeletal strength. Although osteoclast differentiation depends on receptor activator of NFκB ligand (RANKL) stimulation, additional molecules further contribute to osteoclast maturation. Here, we demonstrate that protocadherin-7 (Pcdh7) regulates formation of multinucleated osteoclasts and contributes to maintenance of bone homeostasis. We found that Pcdh7 expression is induced by RANKL stimulation, and that RNAi-mediated knockdown of Pcdh7 resulted in impaired formation of osteoclasts. We generated Pcdh7-deficient mice and found increased bone mass due to decreased bone resorption but without any defect in bone formation. Using an in vitro culture system, it was revealed that formation of multinucleated osteoclasts is impaired in Pcdh7-deficient cultures, while no apparent defects were observed in differentiation and function of Pcdh7-deficient osteoblasts. Taken together, these results reveal an osteoclast cell-intrinsic role for Pcdh7 in maintaining bone homeostasis.