Ming Chen1,2, Hui Han1,2, Siqi Zhou1,2,3, Yinxian Wen4,5, Liaobin Chen6,7. 1. Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. 2. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. 3. Department of Orthopedics Department, Renmin Hospital of Wuhan University, Wuhan, 430060, China. 4. Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. wenyinxian@whu.edu.cn. 5. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. wenyinxian@whu.edu.cn. 6. Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. lbchen@whu.edu.cn. 7. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. lbchen@whu.edu.cn.
Abstract
BACKGROUND: Osteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear. METHODS: BMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry. RESULTS: The results showed the function of 2.5-10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/β-catenin signaling pathway) was added to the Morusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in the rat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo. CONCLUSIONS: This study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.
BACKGROUND:Osteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear. METHODS: BMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry. RESULTS: The results showed the function of 2.5-10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating theWnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of theWnt/β-catenin signaling pathway) was added to theMorusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in therat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo. CONCLUSIONS: This study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.
Authors: David W Dempster; Juliet E Compston; Marc K Drezner; Francis H Glorieux; John A Kanis; Hartmut Malluche; Pierre J Meunier; Susan M Ott; Robert R Recker; A Michael Parfitt Journal: J Bone Miner Res Date: 2013-01 Impact factor: 6.741
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