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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.3
- 수록면
- 234 - 243 (10page)
- DOI
- 10.14348/molcells.2018.2340
이용수
초록· 키워드
오류제보하기
In recent years, the interest towards the relationship between incretins and bone has been increasing. Previous studies have suggested that glucagon-like peptide-1 (GLP-1) and its receptor agonists exert beneficial anabolic influence on skeletal metabolism, such as promoting proliferation and differentiation of osteoblasts via entero-osseous-axis. However, little is known regarding the effects of GLP-1 on osteoblast apoptosis and the underlying mechanisms involved. Thus, in the present study, we investigated the effects of liraglutide, a glucagon-like peptide-1 receptor agonist, on apoptosis of murine MC3T3-E1 osteoblastic cells. We confirmed the presence of GLP-1 receptor (GLP-1R) in MC3T3-E1 cells. Our data demonstrated that liraglutide inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as detected by Annexin V/PI and Hoechst 33258 staining and ELISA assays. Moreover, liraglutide upregulated Bcl-2 expression and downregulated Bax expression and caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further study suggested that liraglutide stimulated the phosphorylation of AKT and enhanced cAMP level, along with decreased phosphorylation of GSK3β, increased β-catenin phosphorylation at Ser675 site and upregulated nuclear β-catenin content and transcriptional activity. Pretreatment of cells with the PI3K inhibitor LY294002, PKA inhibitor H89, and siRNAs GLP-1R, β-catenin abrogated the liraglutideinduced activation of cAMP, AKT, β-catenin, respectively. In conclusion, these findings illustrate that activation of GLP-1 receptor by liraglutide inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation through cAMP/ PKA/β-catenin and PI3K/Akt/GSK3β signaling pathways.
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등록된 정보가 없습니다.
참고문헌 (43)
참고문헌 신청
Ono, T. / 2014 / Expression of glucagon-like peptide-1 receptor and glucosedependent insulinotropic polypeptide receptor is regulated by the glucose concentration in mouse osteoblastic MC3T3-E1 cells / Int J. Mol. Med. 34:475~482
Berlier, J.L. / 2015 / Glucosedependent insulinotropic peptide prevents serum deprivationinduced apoptosis in human bone marrow-derived mesenchymal stem cells and osteoblastic cells / Stem Cell Rev. 11:841~851
Bodine, P.V. / 2006 / Wnt signaling and osteoblastogenesis / Rev. Endocrine Metabol. Dis. 7:33~39
Bullock, B.P. / 1996 / Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor / Endocrinology 137:2968~2978
Campbell, J.E. / 2013 / Pharmacology, physiology, and mechanisms of incretin hormone action / Cell Metabol. 17:819~837
Berlier, J.L. / 2015 / Glucosedependent insulinotropic peptide prevents serum deprivationinduced apoptosis in human bone marrow-derived mesenchymal stem cells and osteoblastic cells / Stem Cell Rev. 11:841~851
Bodine, P.V. / 2006 / Wnt signaling and osteoblastogenesis / Rev. Endocrine Metabol. Dis. 7:33~39
Bullock, B.P. / 1996 / Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor / Endocrinology 137:2968~2978
Campbell, J.E. / 2013 / Pharmacology, physiology, and mechanisms of incretin hormone action / Cell Metabol. 17:819~837
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