Work

Parathyroid hormone ameliorates osteogenesis of human bone marrow mesenchymal stem cells against glucolipotoxicity through p38 MAPK signaling

Year: 2020

Type: article

Abstract: Diabetes mellitus (DM)‐induced glucolipotoxicity is a factor strongly contributing to alveolar bone deficiency. Parathyroid hormone (PTH) has been identified as a main systemic mediator to balance physiological calcium in bone. This study aimed to uncover PTH's potential role in ameliorating the osteogenic capacity of human bone marrow mesenchymal stem cells (HBMSCs) against glucolipotoxicity. Optimal PTH concentrations and high glucose and palmitic acid (GP) were administered to cells, followed by alkaline phosphatase (ALP) staining and ALP activity assay. Quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) and Immunoblot were carried out for assessing mRNA and protein amounts, respectively. Cell counting kit‐8 (CCK‐8) and flow cytometry were performed for quantitating cell proliferation. Osteogenesis and oxidative stress were determined, and the involvement of mitogen‐activated protein kinase (MAPK) signaling was further verified. About 1–50 mmol/ml GP significantly inhibited the osteogenic differentiation of HBMSCs. 10−9 mol/L PTH was found to be the optimal concentration for HBMSC induction. PTH had no effects on HBMSC proliferation, with or without GP treatment. PTH reversed inadequate osteogenesis and excessive oxidative stress in GP‐treated HBMSCs. Mechanistically, PTH activated p38 MAPK signaling, while inhibiting p38 MAPK‐suppressed PTH's beneficial impacts on HBMSCs. Collectively, PTH promotes osteogenic differentiation in HBMSCs against glucolipotoxicity via p38 MAPK signaling.

Source: IUBMB Life

DOI: 10.1002/iub.2420