Abstract: Objective: To investigate the effect of Prader-Willi/Angelman syndrome region protein 2(NIPA2) on the high glucose-induced osteoblast apoptosis, and to elucidate its mechanism; Methods: The osteoblasts MC3T3-E1 were treated with 26 nmol·L^-1 high glucose for 24 h; the cells were divided into HG+si-con group (transfected with si-con), HG+si-NIPA2 group (transfected with si-NIPA2), HG+si-NIPA2+DMSO group (transfected with si-NIPA2 and treated with DMSO), HG+si-NIPA2+AG490 (transfected with si-NIPA2 and treated with AG490),at the same time control group was set up. After the MC3T3-E1 cells were transfected by liposome method, they were treated with 26 nmol·L^-1 high glucose again.The qRT-PCR method was used to detect the expression level of NIPA2 mRNA in theMC3T3-E1 cells;Western blotting method was used to determine the expression levels of NIPA2, P21, Cleaved caspase-3, p-JAK2 and p-STAT3 proteins in the MC3T3-E1 cells; MTT method was used to detect the cell proliferation activities, and flow cytometry was used to measure the apoptotic rates. Results: Compared with control group, the mRNA and protein expression levels of NIPA2 in the MC3T3-E1 cells in HG group were significantly decreased (P<0.01). After knocking down the NIPA2, compared with HG+si-con group, the expression level of NIPA2 protein in HG+si-NIPA2 group was significantly decreased (P<0.01), the expression levels of P21 and Cleaved caspase-3 proteins were significantly increased (P<0.01), the proliferation activities of MC3T3-E1 cells were significantly decreased at 48 and 72 h (P<0.01), the apoptotic rate was significantly increased (P<0.01), and the expression levels of JAK/STAT signaling pathway-related proteins p-JAK2 and p-STAT3 were significantly increased (P<0.01).Compared with HG+si-NIPA2+DMSO group, the expression levels of NIPA2 protein in HG+si-NIPA2+AG490 group was significantly increased (P<0.01), the expression levels of P21 and Cleaved caspase-3 proteins were significantly decreased (P<0.01), the cell proliferation activities were significantly increased at 48 and 72 h (P<0.01), and the apoptotic rate was significantly decreased (P<0.01). Conclusion: NIPA2 can regulate the proliferation and apoptosis of the osteoblasts induced by high glucose, and its regulatory mechanism is related to the JAK/STAT signaling pathway.

Key words: NIPA2, JAK/STAT signaling pathway, osteoblasts, apoptosis