Abstract
BackgroundOsteoporosis (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.MethodsBMSCs 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.ResultsThe 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.ConclusionsThis 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.
Highlights
Osteoporosis (OP), a highly prevalent metabolic bone disease, is featured with reduced bone mineral content in addition to structural degeneration of the skeletal system [1, 2]
Data analysis We indicated all experimental values as mean ± standard error of mean (SEM) of the experimental values
There was promoted proliferation detected in the osteogenic bone marrow mesenchymal stem cells (BMSCs) treated with Morusin at 2.5, 5, and 10 μM (Fig. 1b) in days 3, 5, 7, and 14, while Morusin of 20 μM and 50 μM both showed an inhibitive effect on the proliferation of BMSCs in days 7 and 14
Summary
Osteoporosis (OP), a highly prevalent metabolic bone disease, is featured with reduced bone mineral content in addition to structural degeneration of the skeletal system [1, 2]. The Wnt/β-catenin signaling pathway is a significant classical pathway in osteogenic differentiation of BMSCs [8]. According to the previous reports, the TLR4 deficiency in knockout mice could promote fracture healing and increase bone mass by way of activating the Wnt/β-catenin signaling pathway [11]. Another study revealed that vasoactive intestinal peptide (VIP) promoted the BMSCs osteogenesis in addition to the angiogenesis differentiation in vitro through activating the Wnt/β-catenin signaling pathway, and advanced bone recovery in vivo [12]. All these evidences suggest Wnt/βcatenin signaling pathways are vital for bone mass maintenance, osteogenic differentiation, and promotion of bone repair. Whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear
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