Ming Leiguo, Jin Fang, Huang Ping, Luo Hailang, Liu Wenjia, Zhang Leilei, Yuan Wei, Zhang Yongjie, Jin Yan
1] State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China [2] State Key Laboratory of Military Stomatology, Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China [3] Institute forTissue Engineering and Regenerative Medicine Research of Xi'an, Xi'an, China.
Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Sci Rep. 2014 Nov 27;4:7209. doi: 10.1038/srep07209.
The role of bone marrow-derived mesenchymal stem cells(BMSCs)in the pathogenesis and therapy of osteoporosis has drawn increasing attention in recent years. In the development of osteoporosis, it has been demonstrated that many changes occurred in the behavior of BMSCs. For example, the biological system of FasL pathways mediated differentiation of ERK and GSK-3β-catenin pathway was damaged. Here we found that 0.35 mg/L Licochalcone A (L-A) had a strong effect in increasing the osteogenic differentiation and mineralization of BMSCs both in vivo and in vitro by up-regulating FasL and further playing a role in regulating the ERK and GSK-3β-catenin systems. It has also demonstrated that the administration of L-A could restore the biological function of the damaged BMSCs differentiation by recovering or protecting bone mass in a disease state through activating the endosteal bone formation and partially inhibiting bone resorption in acute estrogen deficiency model. Results of our study suggested that careful titration of MSC was response to L-A and up-regulated FasL pathways mediating differentiation of ERK and GSK-3β-catenin biological systems under disease state in vivo, restore the impaired function, is one of the ways of L-A relieve or treatment osteoporosis.
近年来，骨髓间充质干细胞（BMSCs）在骨质疏松症发病机制及治疗中的作用受到越来越多的关注。在骨质疏松症的发展过程中，已证实BMSCs的行为发生了许多变化。例如，FasL途径介导的ERK和GSK-3β-连环蛋白途径分化的生物系统受损。在此我们发现，0.35mg/L的甘草查耳酮A（L-A）通过上调FasL，进而在调节ERK和GSK-3β-连环蛋白系统中发挥作用，在体内和体外均对增加BMSCs的成骨分化和矿化具有显著效果。研究还表明，在急性雌激素缺乏模型中，通过激活骨内膜骨形成并部分抑制骨吸收，给予L-A可以恢复受损BMSCs分化的生物学功能，在疾病状态下恢复或保护骨量。我们的研究结果表明，在体内疾病状态下，精确滴定间充质干细胞对L-A有反应，并上调介导ERK和GSK-3β-连环蛋白生物系统分化的FasL途径，恢复受损功能，是L-A缓解或治疗骨质疏松症的途径之一。
