PTH(1‑34) activates the migration and adhesion of BMSCs through the rictor/mTORC2 pathway

Abstract

The ability of intermittent parathyroid hormone (1-34) [PTH(1-34)] treatment to enhance bone-implant osseo-integration was recently demonstrated in vivo. However, the mechanisms through which PTH (1-34) regulates bone marrow-derived stromal cells (BMSCs) remain unclear. The present study thus aimed to investigate the effects of PTH(1-34) on the migration and adhesion of, and rictor/mammalian target of rapamycin complex 2 (mTORC2) signaling in BMSCs. In the present study, BMSCs were isolated from Sprague-Dawley rats treated with various concentrations of PTH(1-34) for different periods of time. PTH(1-34) treatment was performed with or without an mTORC1 inhibitor (20 nM rapamycin) and mTORC1/2 inhibitor (10 µM PP242). Cell migration was assessed by Transwell cell migration assays and wound healing assays. Cell adhesion and related mRNA expression were investigated through adhesion assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. The protein expression of chemokine receptors (CXCR4 and CCR2) and adhesion factors [intercellular adhesion molecule 1 (ICAM-1), fibronectin and integrin β1] was examined by western blot analysis. The results revealed that various concentrations (1, 10, 20, 50 and 100 nM) of PTH(1-34) significantly increased the migration and adhesion of BMSCs, as well as the expression of CXCR4, CCR2, ICAM-1, fibronectin and integrin β1. In addition, the p-Akt and p-S6 levels were also upregulated by PTH(1-34). BMSCs subjected to mTORC1/2 signaling pathway inhibition or rictor silencing exhibited a markedly reduced PTH-induced migration and adhesion, while no such effect was observed for the BMSCs subjected to mTORC1 pathway inhibition or raptor silencing. These results indicate that PTH(1-34) promotes BMSC migration and adhesion through rictor/mTORC2 signaling in vitro. Taken together, the results of the present study reveal an important mechanism for the therapeutic effects of PTH(1-34) on bone-implant osseointegration and suggest a potential treatment strategy based on the effect of PTH(1-34) on BMSCs.