S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Master's Degree_의학과)
Activation of farnesoid X receptor enhances osteoblastic differentiation
FXR 활성화가 조골세포 분화에 끼치는 영향
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 의학과 분자유전체의학 전공, 2013. 2. 신찬수.
- Introduction : Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, functions as bile acid sensor in the control of bile acid homeostasis. While FXR has been shown to play an important role in metabolic diseases, including diabetes mellitus, dyslipidemia and atherosclerosis, the role of bile acids in bone remodeling is not clear.
Method : The role of FXR in the regulation of osteoblast differentiation was investigated using a series of bile acids. Endogenous FXR expression was compared between murine mesenchymal cells and pre-osteoblastic cells using RT-PCR. Finally, changes in alkaline phosphatase (ALP) activity were monitored during osteoblastic differentiation of mesenchymal cells after treatment with FXR agonists.
Results : FXR was expressed in mesenchymal stem cells (C3H10T1/2) and pre-osteoblastic cells (MC3T3.E1), and gradually increased during osteoblastic differentiation. ALP activity was increased in C3H10T1/2 cells cultured in osteogenic medium and treated with blie acids (6-ethylchenodeoxycholic acid (6-ECDCA) and chenodeoxycholic acid (CDCA)) or synthetic FXR agonists (GW4064 and fexaramine). In addition, mRNA expression levels of the COL1, ALP, BSP, Runx2 and Osx genes were significantly increased by treatment of C3H10T1/2 cells with bile acids (6-ECDCA or CDCA) or FXR agonists (GW4064 or fexaramine).
Conclusion : These results indicate that activation of FXR may enhance osteoblastic differentiation.