Hypoxia suppresses osteogenesis of bone mesenchymal stem cells via the extracellular signal‑regulated 1/2 and p38‑mitogen activated protein kinase signaling pathways

  • Authors:
    • Peng Zhang
    • Nayoung Ha
    • Qinggang Dai
    • Siru Zhou
    • Chuangqi Yu
    • Lingyong Jiang
  • View Affiliations

  • Published online on: August 17, 2017     https://doi.org/10.3892/mmr.2017.7276
  • Pages: 5515-5522
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Abstract

There is a growing body of evidence indicating an association between osteoporosis and vascular diseases, which are associated with reduced blood supply. Decreased vascular flow results in a hypoxic gradient in the local microenvironment, affecting local bone remodeling. Bone mesenchymal stem cells (BMSCs) have been demonstrated to be the key to bone remodeling. To elucidate the molecular mechanisms involved in vascular supply and osteoporosis, the present study investigated the effect of hypoxia on BMSCs in vitro during osteogenesis. The BMSC osteogenesis process was evaluated by alkaline phosphatase (ALP) activity assay and the mRNA expression of the osteogenic markers runt‑related transcription factor 2 (Runx2), ALP and osteocalcin. The function of extracellular signal‑regulated kinase (ERK)1/2 and p38 kinase were studied under hypoxia using specific inhibitors. The results demonstrated that hypoxia reduces the osteogenic differentiation of BMSCs by inactivating Runx2, followed by decreased ALP activity and mRNA expression levels of ALP, collagen type I and osteocalcin. Furthermore, these data suggested that the ERK1/2 and p38‑mitogen activated protein kinase signaling pathways might participate in hypoxia‑induced differentiation of BMSCs toward the osteogenic phenotype. Compared with ERK1/2, the p38‑Runx2 signaling pathway might exert a relatively more prominent effect in the above process. These findings may help to elucidate the pathophysiology of osteoporosis caused by decreased vascular supply.

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October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhang P, Ha N, Dai Q, Zhou S, Yu C and Jiang L: Hypoxia suppresses osteogenesis of bone mesenchymal stem cells via the extracellular signal‑regulated 1/2 and p38‑mitogen activated protein kinase signaling pathways. Mol Med Rep 16: 5515-5522, 2017
APA
Zhang, P., Ha, N., Dai, Q., Zhou, S., Yu, C., & Jiang, L. (2017). Hypoxia suppresses osteogenesis of bone mesenchymal stem cells via the extracellular signal‑regulated 1/2 and p38‑mitogen activated protein kinase signaling pathways. Molecular Medicine Reports, 16, 5515-5522. https://doi.org/10.3892/mmr.2017.7276
MLA
Zhang, P., Ha, N., Dai, Q., Zhou, S., Yu, C., Jiang, L."Hypoxia suppresses osteogenesis of bone mesenchymal stem cells via the extracellular signal‑regulated 1/2 and p38‑mitogen activated protein kinase signaling pathways". Molecular Medicine Reports 16.4 (2017): 5515-5522.
Chicago
Zhang, P., Ha, N., Dai, Q., Zhou, S., Yu, C., Jiang, L."Hypoxia suppresses osteogenesis of bone mesenchymal stem cells via the extracellular signal‑regulated 1/2 and p38‑mitogen activated protein kinase signaling pathways". Molecular Medicine Reports 16, no. 4 (2017): 5515-5522. https://doi.org/10.3892/mmr.2017.7276