Department of Pharmacology, School of Pharmacy & Minhang Hospital, Fudan University, Shanghai 201203, China.
These authors contributed equally to this work.
Mol Cells. 2021 Aug 31;44(8):557-568. doi: 10.14348/molcells.2021.0004.
Global knockout of the BK channel has been proven to affect bone formation; however, whether it directly affects osteoblast differentiation and the mechanism are elusive. In the current study, we further investigated the role of BK channels in bone development and explored whether BK channels impacted the differentiation and proliferation of osteoblasts via the canonical Wnt signaling pathway. Our findings demonstrated that knockout of Kcnma1 disrupted the osteogenesis of osteoblasts and inhibited the stabilization of β-catenin. Western blot analysis showed that the protein levels of Axin1 and USP7 increased when Kcnma1 was deficient. Together, this study confirmed that BK ablation decreased bone mass via the Wnt/β-catenin signaling pathway. Our findings also showed that USP7 might have the ability to stabilize the activity of Axin1, which would increase the degradation of β-catenin in osteoblasts.
全局敲除 BK 通道已被证明会影响骨形成；然而，其是否直接影响成骨细胞分化以及其中的机制仍难以捉摸。在本研究中，我们进一步研究了 BK 通道在骨骼发育中的作用，并探讨了 BK 通道是否通过经典 Wnt 信号通路影响成骨细胞的分化和增殖。我们的研究结果表明，敲除 Kcnma1 破坏了成骨细胞的成骨作用，并抑制了β-连环蛋白的稳定。Western blot 分析表明，当 Kcnma1 缺失时，Axin1 和 USP7 的蛋白水平增加。总之，这项研究证实了 BK 缺失通过 Wnt/β-连环蛋白信号通路减少了骨量。我们的研究结果还表明，USP7 可能具有稳定 Axin1 活性的能力，从而增加成骨细胞中β-连环蛋白的降解。
