Kim Hyunsoo, Takegahara Noriko, Choi Yongwon
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cells. 2025 Aug 21;14(16):1298. doi: 10.3390/cells14161298.
Protocadherin-7 (Pcdh7) is a member of the protocadherin family, a subgroup of the cadherin superfamily. We previously demonstrated that Pcdh7 functions as a signaling receptor in osteoclast differentiation. In this study, we investigated the potential gene regulatory role of Pcdh7 in this process and identified Pyrin domain-containing protein 3 (Pydc3) as a key mediator of Pcdh7-mediated regulation of osteoclast differentiation. Differential gene expression analysis comparing wild-type (Pcdh7) and Pcdh7-deficient (Pcdh7) cells revealed a significant upregulation of in Pcdh7 cells. RNAi-mediated knockdown of rescued the impaired osteoclast differentiation in Pcdh7 cells, whereas overexpression of suppressed osteoclast differentiation in Pcdh7 cells, suggesting that Pydc3 negatively regulates osteoclast differentiation. Additionally, Pcdh7 cells showed elevated expression of interferon response genes and increased production of interferon-β (IFN-β). Neutralization of IFN-β signaling using anti-IFN-β and/or anti-interferon alpha and beta receptor 1 (IFNAR1) antibodies significantly restored osteoclast differentiation in Pcdh7 cells. Collectively, these findings uncover a novel role for Pcdh7 in osteoclast differentiation through regulation of expression and IFN-β production.
原钙黏蛋白-7（Pcdh7）是原钙黏蛋白家族的成员，属于钙黏蛋白超家族的一个亚群。我们之前证明Pcdh7在破骨细胞分化中作为信号受体发挥作用。在本研究中，我们调查了Pcdh7在此过程中潜在的基因调控作用，并确定含吡喃结构域蛋白3（Pydc3）是Pcdh7介导的破骨细胞分化调控的关键介质。比较野生型（Pcdh7）和Pcdh7缺陷型（Pcdh7）细胞的差异基因表达分析显示，Pcdh7细胞中 显著上调。RNAi介导的 敲低挽救了Pcdh7细胞中受损的破骨细胞分化，而 的过表达抑制了Pcdh7细胞中的破骨细胞分化，表明Pydc3负向调节破骨细胞分化。此外，Pcdh7细胞显示出干扰素反应基因表达升高以及干扰素-β（IFN-β）产生增加。使用抗IFN-β和/或抗干扰素α和β受体1（IFNAR1）抗体中和IFN-β信号显著恢复了Pcdh细胞中的破骨细胞分化。总体而言，这些发现揭示了Pcdh7通过调节 表达和IFN-β产生在破骨细胞分化中的新作用。
