GPR39 agonist TC-G 1008 promotes osteoblast differentiation and mineralization in MC3T3-E1 cells
| Autor: | Xingyu Chai, Wencan Zhang, Bingying Chang, Xianli Feng, Jiang Song, Le Li, Chenxiao Yu, Junyong Zhao, Haipeng Si |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Artificial Cells, Nanomedicine, and Biotechnology, Vol 47, Iss 1, Pp 3569-3576 (2019) |
| Druh dokumentu: | article |
| ISSN: | 21691401 2169-141X 2169-1401 |
| DOI: | 10.1080/21691401.2019.1649270 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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