Effect of Bisphosphonates on Osteogenic Potential of Mandibular vs. Long-bone Mesenchymal Stem Cells in Rats

doi:10.3969/j.issn.1005-4979.2016.04.003

Abstract

Abstract: Objective: To investigate the effects of zoledronate， a third generation of bisphosphonates commonly used in clinical practice，on the proliferation and osteogenic differentiation potential of mandibular and long-bone mesenchymal stem cells (BMSCs) in rats. As well as, to study the discrepancy of drug response to biological characteristics of cells derived from distinct skeletal sites. Methods: The BMSCs isolated from the mandible and ilium bone of SD newborn rats were cultured with different concentrations of zoledronate. At 3 days after zoledronate exposure, Alarmar Blue assay was used to measure the absorbance to determine the effect of zoledronate on the proliferation of mandible and ilium mesenchymal stem cells. Cell alkaline phosphatase activity and osteocalcin secretion of mandible and ilium BMSCs were analyzed. Results: Zoledronate at the concentration of ≥2.0 μg/mL could inhibit the proliferation of ilium BMSCs, but it had no effect at the concentration of ≤1.0 μg/mL. For mandible BMSCs, zoledronate at the concentration of ≤0.5 μg/mL inhibited the cell proliferation significantly. Zoledronate (1.0 μg/mL) could also inhibit cell alkaline phosphatase activity, osteocalcin secretion of mandible BMSCs, but at the same concentration, it had no effect to ilium BMSCs. Conclusion: Our findings support that function and differentiation potential of BMSCs derived from distinct origins after exposure to zoledronate is discrepant, and provide a new theoretical basis to clarify pathogenesis of bisphosphonates related osteonecrosis of the jaw (BRONJ).

Key words: bisphosphonates, mandible, ilium, bone mesenchymal stem cells, proliferation, osteogenic differentiation

摘要： 目的：研究临床常用第三代双膦酸盐——唑来膦酸，对大鼠颌面骨及外周骨两种来源的骨髓间充质干细胞(BMSCs)增殖及成骨分化的影响。方法：从新生SD大鼠中分离和培养颌骨或髂骨来源的BMSCs，观察不同浓度唑来膦酸对2种来源BMSCs的影响。观察较高浓度的唑来膦酸对这2种细胞碱性磷酸酶活性、骨钙素分泌的影响。结果：髂骨来源的BMSCs在唑来膦酸浓度≥2.0 μg/mL时增殖受到抑制，浓度≤1.0 μg/mL时增殖不受影响。而颌骨来源的BMSCs，当唑来膦酸浓度≥0.5 μg/mL时细胞增殖就已受到明显的抑制。较高浓度的唑来膦酸（1.0 μg/mL）可抑制颌骨BMSCs碱性磷酸酶的活性以及骨钙素形成；但此浓度，对于髂骨BMSCs碱性磷酸酶活性、骨钙素的形成并没有明显的影响。结论：双膦酸盐对不同来源的BMSCs增殖和成骨分化的影响有差异，可为探索双膦酸盐相关颌骨坏死的发病机制提供理论基础。

关键词: 双膦酸盐, , , 颌骨, , , 髂骨, , , 骨髓间充质干细胞, , , 增殖, , , 成骨分化

CLC Number:

R782
Q813.1

YU Wan-lu, SU Jian-sheng. Effect of Bisphosphonates on Osteogenic Potential of Mandibular vs. Long-bone Mesenchymal Stem Cells in Rats[J]. 《Journal of Oral and Maxillofacial Surgery》, 2016, 26(4): 244-250.

俞宛璐，苏俭生. 双膦酸盐对大鼠颌面骨及外周骨不同来源骨髓间充质干细胞成骨分化的影响[J]. 《口腔颌面外科杂志》, 2016, 26(4): 244-250.

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URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.3969/j.issn.1005-4979.2016.04.003

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2016/V26/I4/244

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