Exendin-4 promotes proliferation and differentiation of MC3T3-E1 osteoblasts by MAPKs activation

    1. Lingling Xiu1
    1. 1Department of Endocrinology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
    2. 2Department of Geriatrics, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
    3. 3Department of Endocrinology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China
    1. Correspondence should be addressed to L Xiu; Email: xlingling58{at}163.com


    Glucagon-like peptide-1 (GLP1) and its receptor agonist have been previously reported to play a positive role in bone metabolism in aged ovariectomized rats and insulin-resistant models. However, whether GLP1 has a direct effect on the proliferation and differentiation of osteoblasts or any cellular mechanism for this potential role is unknown. We examined the effects of the GLP1 receptor agonist exendin-4 on the proliferation, differentiation, and mineralization of mouse osteoblastic MC3T3-E1 cells. GLP1 receptor was detected in MC3T3-E1 cells by polymerase chain reaction (PCR) and Western blot assay. Cell proliferation was assessed using MTT assay, revealing that exendin-4 increased cell proliferation at effective concentrations between 10−10 and 10−5 M. Quantitative PCR analysis showed that exendin-4 increased the mRNA expression of the differentiation markers alkaline phosphatase (ALP), collagen-1 (COL1), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2) under osteogenic conditions. Alizarin red staining confirmed that 10−7 M exendin-4 increased osteoblast mineralization by 18.7%. Exendin-4 upregulated the phosphorylation of ERK1/2, p38, and JNK, with the peak effect at 1.5 h in the Western blot analysis. The use of selective MAPK inhibitors, namely PD98059, SB203580, and SP600125, blocked the effects of exendin-4 on kinase activation (ERK1/2, p38, and JNK), as well as cell proliferation and differentiation in MC3T3-E1 cells. These findings demonstrate that exendin-4 promotes both the proliferation and differentiation of preosteoblasts MC3T3-E1 via activation of the MAPK pathway.

    • Received 24 November 2015
    • Accepted 2 December 2015
    • Made available online as an Accepted Preprint 1 April 2016
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    1. J Mol Endocrinol 56 189-199
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