Abstract
Succinate receptor GPR91 is one of the G protein-coupled receptors (GPCRs) that interacts with various proteins to regulate diverse cellular functions such as cell morphology, apoptosis, and differentiation. In this study, we investigated whether the GPR91-mediated signaling pathway regulates mineralization in Porphyromonas gingivalis (P. gingivalis)-treated osteoblasts and to determine its potential role in osteoclast differentiation. Primary mouse osteoblasts from wild-type (WT) and GPR91 knockout (GPR91-/-) mice infected with P. gingivalis were used for in vitro experiments. The results showed that inhibition by 4C, a specific inhibitor, and GPR91 knockout promoted mineralization in P. gingivalis-infected osteoblasts. Surprisingly, GPR91 knockdown decreased the migration ability of osteoblasts. Moreover, compared with P. gingivalis-infected WT osteoblasts, GPR91-/- osteoblasts exhibited decreased RANKL production, and conditioned media (CM) from bacteria-infected GPR91-/- osteoblasts suppressed the formation of osteoclast precursors. Moreover, P. gingivalis mediated the role of GPR91 in osteoblast mineralization by activating the NF-κB pathway. These findings suggest that GPR91 activation reduces mineralization of P. gingivalis-infected osteoblasts and promotes osteoclastogenesis in macrophages. Therefore, targeting GPR91 may mitigate the loss of alveolar bone during bacterial infection.