Abstract
TRPM7 is a member of the transient receptor potential cation channel (TRP channel) subfamily M and possesses both an ion channel domain and a functional serine/threonine α-kinase domain. It has been proven to play an essential role in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). However, the signaling pathway and molecular mechanism for TRPM7 in regulating osteogenic differentiation remain largely unknown. In this study, the potential role and mechanism of TRPM7 in the osteogenic differentiation of hBMSCs were investigated. The results showed that the expression of TRPM7 mRNA and protein increased, as did the osteogenic induction time. Upregulation or inhibition of TRPM7 could promote or inhibit the osteogenic differentiation of hBMSCs for 14 days. It was also found that the upregulation or inhibition of TRPM7 promoted or inhibited the activity of PLC and SMAD1, respectively, during osteogenic differentiation. PLC could promote osteogenic differentiation by upregulating the activity of SMAD1. However, inhibition of PLC alone could reduce the activity of SMAD1 but not inhibit completely the activation of SMAD1. Therefore, we inferred that it is an important signaling pathway for TRPM7 to upregulate the activity of SMAD1 through PLC and thereby promote the osteogenic differentiation of hBMSCs, but it is not a singular pathway. TRPM7 may also regulate the activation of SMAD1 through other ways, except for PLC, during osteogenic differentiation of hBMSCs.