A Novel Role of Protecadherin-7 in Regulation of Pydc3 Expression and the IFN-β Response During Osteoclast Differentiation.

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.