GPR39 agonist TC-G 1008 promotes osteoblast differentiation and mineralization in MC3T3-E1 cells

• Published in: Artificial cells, nanomedicine, and biotechnology Vol. 47; no. 1; pp. 3569 - 3576
• Main Authors: Chai, Xingyu, Zhang, Wencan, Chang, Bingying, Feng, Xianli, Song, Jiang, Li, Le, Yu, Chenxiao, Zhao, Junyong, Si, Haipeng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2019; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: 3T3 Cells; Agonists; Alkaline phosphatase; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Biomedical materials; Bone growth; Bone remodeling; Calcium; Cell activation; Cell culture; Cell differentiation; Cell Differentiation - drug effects; Cell Line; Collagen (type I); Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Culture media; Deposition; Enzyme Activation - drug effects; Gene Expression Regulation - drug effects; GPR39; MC3T3-E1; Metabolic pathways; Mice; Mineralization; Minerals - metabolism; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type III - metabolism; osteoblast differentiation; Osteoblastogenesis; Osteoblasts; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteocalcin; Osteogenesis; Osteogenesis - drug effects; Osteoporosis; Phosphorylation - drug effects; Pyrimidines - pharmacology; Receptors, G-Protein-Coupled - agonists; Runx-2; Sulfonamides - pharmacology; TC-G 1008; Therapeutic applications; GPR39; AMPK; Runx-2; TC-G 1008; osteoblast differentiation; MC3T3-E1
• ISSN: 2169-1401; 2169-141X; 2169-141X
• DOI: 10.1080/21691401.2019.1649270

Osteoporosis-related bone fracture and falls have a severe impact on patients' daily lives. Osteoblasts are bone-building cells that play a vital role in bone formation and remodeling. Imbalanced osteoblast differentiation could lead to osteoporosis. GPR39 is an orphan G protein-coupled receptor that mediates metabolic pathways. In this study, we show that GPR39 is expressed in MC3T3-E1 cells. Osteoblast differentiation culture media induces GPR39, suggesting that GPR39 is a differentiation-responsive factor. Activation of GPR39 using its selective agonist TC-G 1008 induces alkaline phosphatase (ALP), osteocalcin (OCN), and type I collagen (Col-I) expression, and increases cellular ALP activity and calcium deposition, implying that GPR activation promotes cells toward osteoblast differentiation. Treatment with TC-G 1008 also increases Runx-2 expression and AMPK activation. However, the inhibition of AMPK by Compound C abolished TC-G 1008-mediated ALP, OCN, and Col-I induction, and reduces ALP activity and cellular calcium deposition as well as Runx-2 induction. These data indicate that TC-G 1008-mediated GPR39 activation involves AMPK-mediated Runx-2 induction. In summary, our study uncovers a new role of GPR39 activation in osteoblast differentiation, implying that GPR39 could be a promising therapeutic target for osteoporosis.