2. Academic Validation
  3. AMD3465 (hexahydrobromide) rescues the MG63 osteoblasts against the apoptosis induced by high glucose

AMD3465 (hexahydrobromide) rescues the MG63 osteoblasts against the apoptosis induced by high glucose

  • Biomed Pharmacother. 2021 Jun;138:111476. doi: 10.1016/j.biopha.2021.111476.
Zhongwen Zhang 1,  Hongxia Wu 1,  Shuhong Huang 2,  Liping Chen 3,  Xinlong Chen 4,  Wei Zhang 1,  Lin Liao 1,  Xiaoqian Zhang 5
Affiliations

Affiliations

  • 1 Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan 250014, Shandong, China.
  • 2 Institute of Basic Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan 250012, Shandong, China.
  • 3 Department of Endocrinology, Weifang Medical University, Weifang 261053, China.
  • 4 Department of dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan, China.
  • 5 Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan 250014, Shandong, China; Department of Endocrinology, Weifang Medical University, Weifang 261053, China. Electronic address: [email protected].
PMID: 33773470 DOI: 10.1016/j.biopha.2021.111476
Abstract

Diabetic osteoporosis (DOP) is a serious complication of diabetes, which brings a heavy burden to patients' families and society. The SDF-1/CXCR4 signal pathway may be a target to prevent articular cartilage degeneration. In this study, we studied the effects of high glucose (20 mmol/L) and CXCR4 Antagonist AMD3465 (10 μmol/L) on the Apoptosis and gene expression of osteoblast-like cells MG63 to determine a new treatment for DOP. CCK8 and clone formation assays confirmed that AMD3465 resisted the decrease of proliferation caused by high glucose. According to the results of scratch and transwell analysis, AMD3465 could remedy the decrease of cell migration and invasion induced by high glucose. The results of flow cytometry analysis and double staining with Hoechst and PI showed AMD3465 corrected the Apoptosis induced by high glucose. In addition, high glucose regulated the expression of cell cycle- and apoptosis-related proteins, while AMD3465 blocked the regulation of high glucose. Furthermore, high glucose enhanced the expression levels of SDF-1 and CXCR4 in MG63 cells, as well as the release of MMP1, 3, 9 and 13. AMD3465 inhibited the release of MMPs. The results showed that AMD3465 resisted the Apoptosis of MG63 cells induced by high glucose, provided a new strategy for the therapy of DOP.

Keywords

AMD3465; Apoptosis; CXCR4; Diabetic osteoporosis; MG63 cell.

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