Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;235(6):5182-5191.
doi: 10.1002/jcp.29395. Epub 2019 Nov 19.

Mg2+ in β-TCP/Mg-Zn composite enhances the differentiation of human bone marrow stromal cells into osteoblasts through MAPK-regulated Runx2/Osx

Zhenting Wang  1   2   3 , Qing Liu  3 , Congcong Liu  3 , Wei Tan  3 , Mingying Tang  1 , Xiaohua Zhou  1 , Tianshi Sun  1 , Youwen Deng  1   3
Affiliations

Mg2+ in β-TCP/Mg-Zn composite enhances the differentiation of human bone marrow stromal cells into osteoblasts through MAPK-regulated Runx2/Osx

Zhenting Wang et al. J Cell Physiol. 2020 Jun.

Abstract

Inducing the osteogenic differentiation from bone marrow stromal cells (BMSCs) might be a potent strategy for treating bone loss and nonunion during fracture and improving fracture healing. Among several signaling pathways involved, mitogen-activated protein kinases (MAPKs) have been reported to play a critical role. Magnesium (Mg)-based alloys, including Mg-Zn alloy, have been used clinically as implants in the musculoskeletal field and could promote BMSC osteogenic differentiation. However, the underlying mechanisms remain unclear. In this study, we produced Mg-Zn alloy consists of Mg and low concentrations of Zn, calcium carbonate, and β-tricalcium phosphate (β-TCP; manifesting process not shown), prepared Mg, Zn, and Mg-Zn extracts, and investigated the specific effects of these extracts on human BMSC (hBMSC) osteogenic differentiation and MAPK signaling. Mg extracts and Mg-Zn extracts could significantly promote the osteogenic differentiation of hBMSCs as manifested as increased alkaline phosphatase levels, enhanced calcium nodules formation, and increased messenger RNA expression and protein levels of osteogenesis markers, including BMPs, Col-I, Runx2, and Osx; in the meantime, Mg culture medium (CM) and Mg-Zn CM both significantly enhanced the activation of MAPK signaling in hBMSCs. By adding ERK1/2 signaling, p38 signaling, or JNK signaling inhibitor to Mg-Zn CM, or conducting p38 MAPK silence in hBMSCs, we revealed that these extracts might promote hBMSC osteogenic differentiation via p38 MAPK signaling and MAPK-regulated Runx2/Osx. In conclusion, Mg2+ in β-TCP/Mg-Zn extract promotes the osteogenic differentiation of hBMSCs via MAPK-regulated Runx2/Osx interaction.

Keywords: MAPK; Mg alloy; Runx2/Osx; bone marrow stromal cells (BMSCs); fracture healing; osteogenic differentiation.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Addison, W. N., Azari, F., Sorensen, E. S., Kaartinen, M. T., & McKee, M. D. (2007). Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, up-regulating osteopontin, and inhibiting alkaline phosphatase activity. Journal of Biological Chemistry, 282(21), 15872-15883.
    1. Artigas, N., Urena, C., Rodriguez-Carballo, E., Rosa, J. L., & Ventura, F. (2014). Mitogen-activated protein kinase (MAPK)-regulated interactions between Osterix and Runx2 are critical for the transcriptional osteogenic program. Journal of Biological Chemistry, 289(39), 27105-27117.
    1. Burmester, A., Luthringer, B., Willumeit, R., & Feyerabend, F. (2014). Comparison of the reaction of bone-derived cells to enhanced MgCl2-salt concentrations. Biomatter, 4, e967616.
    1. Caverzasio, J., & Manen, D. (2007). Essential role of Wnt3a-mediated activation of mitogen-activated protein kinase p38 for the stimulation of alkaline phosphatase activity and matrix mineralization in C3H10T1/2 mesenchymal cells. Endocrinology, 148(11), 5323-5330.
    1. Chang, L., & Karin, M. (2001). Mammalian MAP kinase signalling cascades. Nature, 410(6824), 37-40.

Publication types

MeSH terms

LinkOut - more resources