miR-23b-3p regulates differentiation of osteoclasts by targeting PTEN via the PI3k/AKT pathway

INTRODUCTION: Osteoblasts and osteoclasts are cells of osteoblastic origin, and are vital in homeostasis of the skeleton. miRs are important for functioning, survival and differentiation of osteoclasts. It has been reported previously that miR-23b-3p is involved in osteoporosis and in regulation of differentiation of osteoblasts. It is also involved in the process of bone formation. However, the role of miR-23b-3p in differentiation of osteoclasts remains unexplored. MATERIAL AND METHODS: CSF-1 and ODF induced osteoclasts were used for the study. RNA isolation was done from TIB-71 cells. TRAP staining was done for TRAP-positive osteoclast formation. PIT assay for bone resorption was performed. For in vivo studies osteoclast-specific miR-23b-3p transgenic mice were developed. RESULTS: The levels of miR-23b-3p were upregulated in bone marrow monocytes during osteoclastogenesis with colony stimulating factor-1 and osteoclast differentiation factor induction, which suggests that miR-23b-3p plays a crucial role in differentiation of osteoclasts. Over-expression of miR-23b-3p in bone marrow monocytes leads to osteoclastogenesis, whereas the inhibition ameliorates it. We further studied the function of miR-23b-3p via PI3K/AKT targeting the PTEN pathway. In vivo, osteoclast-specific miR-23b-3p transgenic mice showed suppressed PTEN and elevated osteoclast activity, and the mice showed decreased bone mineral density. CONCLUSIONS: The results suggest that miR-23b-3p regulates the differentiation of osteoclasts by targeting PTEN through the PI3K/AKT cascade.