PMID- 33712069 OWN - NLM STAT- MEDLINE DCOM- 20210708 LR - 20240331 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 12 IP - 1 DP - 2021 Mar 12 TI - Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/beta-catenin pathway and prevents bone loss in an ovariectomized rat model. PG - 173 LID - 10.1186/s13287-021-02239-3 [doi] LID - 173 AB - 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/beta-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 muM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/beta-catenin signaling pathway via inhibition of beta-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/beta-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/beta-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment. FAU - Chen, Ming AU - Chen M AD - Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. FAU - Han, Hui AU - Han H AD - Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. FAU - Zhou, Siqi AU - Zhou S AD - Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. AD - Department of Orthopedics Department, Renmin Hospital of Wuhan University, Wuhan, 430060, China. FAU - Wen, Yinxian AU - Wen Y AD - Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. wenyinxian@whu.edu.cn. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. wenyinxian@whu.edu.cn. FAU - Chen, Liaobin AU - Chen L AD - Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. lbchen@whu.edu.cn. AD - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. lbchen@whu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210312 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Flavonoids) RN - 0 (beta Catenin) RN - 62596-29-6 (morusin) SB - IM MH - Animals MH - Bone Marrow Cells/metabolism MH - Cell Differentiation MH - Cells, Cultured MH - Female MH - Flavonoids MH - *Mesenchymal Stem Cells/metabolism MH - Osteogenesis MH - *Osteoporosis MH - Rats MH - Rats, Wistar MH - Wnt Signaling Pathway MH - beta Catenin/genetics/metabolism PMC - PMC7953707 OTO - NOTNLM OT - BMSCs OT - Morusin OT - Osteoporosis OT - Wnt/beta-catenin COIS- The authors declare that they have no competing interests. EDAT- 2021/03/14 06:00 MHDA- 2021/07/09 06:00 PMCR- 2021/03/12 CRDT- 2021/03/13 05:32 PHST- 2021/01/22 00:00 [received] PHST- 2021/02/24 00:00 [accepted] PHST- 2021/03/13 05:32 [entrez] PHST- 2021/03/14 06:00 [pubmed] PHST- 2021/07/09 06:00 [medline] PHST- 2021/03/12 00:00 [pmc-release] AID - 10.1186/s13287-021-02239-3 [pii] AID - 2239 [pii] AID - 10.1186/s13287-021-02239-3 [doi] PST - epublish SO - Stem Cell Res Ther. 2021 Mar 12;12(1):173. doi: 10.1186/s13287-021-02239-3.