The involvement of senescence induced by the telomere shortness in the decline of osteogenic differentiation in BMSCs

C. Li, G.-J. Wei, L. Xu, J.-S. Rong, S.-Q. Tao, Y.-S. Wang

Department of Orthopedics, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China. yansongwang0001@163.com

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• Pharmacology

OBJECTIVE: BMSC (Bone marrow mesenchymal stem cells) is an important seed cell for the repair of bone and cartilage defect in the tissue engineering. The proliferation rate and differentiation capacity of BMSCs from the old donors were less than that from young donors; however, the related mechanism remained unclear.

MATERIALS AND METHODS: Sprague Dawley (SD) rats BMSCs were cultured and treated. Hydrogen peroxide (H2O2) and continual passage of BMSCs were performed to induce senescence. Senescence was detected by the SA-b-Gal staining and the telomere length analysis. Cell proliferation and osteogenic differentiation were also observed. Finally, Olaparib was used to maintain the telomere length and investigate the role of telomere length and senescence on the cell proliferation and differentiation.

RESULTS: H2O2 could increase the positive rate of SA-b-Gal staining in BMSCs and shorten the length of the telomere. The proliferation rate and ALP activity were also decreased by the H2O2. The senescence and decline of osteogenic differentiation could also be observed after prolonged passage of BMSCs. Inhibition of telomere length decline could attenuate the increased positive rate of SA-b-Gal staining induced by the H2O2, promote the cell proliferation, and enhance the capacity of osteogenic differentiation.

CONCLUSIONS: Senescence induced by the decline of telomere length could reduce the capacity of osteogenic differentiation and inhibit cell proliferation in BMSCs.

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