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  2. NIPA2 regulates osteoblast function via its effect on apoptosis pathways in type 2 diabetes osteoporosis

NIPA2 regulates osteoblast function via its effect on apoptosis pathways in type 2 diabetes osteoporosis

  • Biochem Biophys Res Commun. 2019 Jun 11;513(4):883-890. doi: 10.1016/j.bbrc.2019.04.030.
Wei Zhao 1 Wei-Lin Zhang 2 Bo Yang 1 Jun Sun 1 Mao-Wei Yang 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning, China.
  • 2 Department of Orthopedics, The Fourth Hospital of China Medical University, Shenyang, Liaoning, China.
  • 3 Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address: mwyang@cmu.edu.cn.
Abstract

Type 2 diabetes osteoporosis has recently become a hot topic in the study of diabetic complications, but the specific mechanism of its development remains unclear. Non-imprinted in Prader-Willi/Angelman syndrome region protein 2 (NIPA2), a highly-selective magnesium ion transporter, has been found to be associated with type 2 diabetes. In this study we aimed to investigate the specific role and mechanism of NIPA2 in the pathogenesis of type 2 diabetes osteoporosis. We first used western blotting, PCR, immunofluorescence, and magnesium ion probes to detect changes of NIPA2 and intracellular magnesium levels in osteoblasts at different concentrations of advanced glycation end products (AGEs). We then up- or down-regulated NIPA2 using a lentivirus and analyzed apoptotic biomarkers as well as the osteogenic ability of osteoblasts. We found that AGEs dose-dependently down-regulated the expression of NIPA2 in osteoblasts. NIPA2 also regulated osteoblast Apoptosis by affecting the intracellular magnesium level and further affecting the osteogenic capacity of osteoblasts. Our study revealed the changes of NIPA2 in response to AGEs in the environment, as well as its function and mechanism in osteoblasts, demonstrating its important role in the pathogenesis of type 2 diabetes osteoporosis. The study suggests that NIPA2 is a potential target for the treatment of type 2 diabetes osteoporosis.

Keywords

Apoptosis; Magnesium; NIPA2; Osteoblast; Type 2 diabetes osteoporosis.

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