Restoration of osteogenic differentiation by overexpression of cannabinoid receptor 2 in bone marrow mesenchymal stem cells isolated from osteoporotic patients.

Cannabinoid receptor 2 (CNR2) has a critical role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). CNR2 expression was found to be downregulated in osteoporotic patients. The present study aimed to investigate the functionality of CNR2 in restoring osteogenic differentiation and mineralization of BMSCs isolated from osteoporotic patients. CNR2 was overexpressed in osteoporotic BMSCs by a lentivirus. Alkaline phosphatase (ALP) activity staining and alizarin red S staining were performed to examine the osteogenic differentiation of osteoporotic BMSCs. Reverse-transcription quantitative polymerase chain reaction analysis was performed to examine the expression of osteogenic genes in BMSCs. Western blot analysis was used to study the activation of p38 mitogen-activated protein kinase (MAPK) during osteogenic differentiation of osteoporotic BMSCs after lentivirus-mediated overexpression of CNR2. The results demonstrated that overexpression of CNR2 in osteoporotic BMSCs increased ALP activity, promoted expression of osteogenic genes and enhanced deposition of mineralized extracellular matrix. In addition, phosphorylation of p38 MAPK was found to be increased by overexpression of CNR2. In conclusion, the present study indicated that restoration of CNR2 recovered the osteogenic differentiation of BMSCs isolated from osteoporotic patients. This finding may provide a novel strategy for a treatment approach for osteoporosis.