DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis

Abstract

As one of the leading causes of bone fracture in postmenopausal women and in older men, osteoporosis worldwide is attracting more attention in recent decades. Osteoporosis is a common disease mainly resulting from an imbalance of bone formation and bone resorption. Pharmaceutically active compounds that both activate osteogenesis, while repressing osteoclastogenesis hold the potential of being therapeutic medications for osteoporosis treatment. In the present study, sesamin, a bioactive ingredient derived from the seed of Sesamum Indicum, was screened out from a bioactive compound library and shown to exhibit dual-regulating functions on these two processes. Sesamin was demonstrated to promote osteogenesis by upregulating Wnt/β-catenin, while repressing osteoclastogenesis via downregulating NF-κB signaling . Furthermore, DANCR was found to be the key regulator in sesamin-mediated bone formation and resorption . In an ovariectomy (OVX)-induced osteoporotic mouse model, sesamin could rescue OVX-induced bone loss and impairment. The increased serum level of DANCR caused by OVX was also downregulated upon sesamin treatment. In conclusion, our results demonstrate that sesamin plays a dual-functional role in both osteogenesis activation and osteoclastogenesis de-activation in a DANCR-dependent manner, suggesting that it may be a possible medication candidate for osteoporotic patients with elevated DNACR expression levels.

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation

“…Sesamin, a member of the lignan family, has estrogenic activity and plays an important role in healing osteoporotic fracture by activating angiogenesis and chondrogenesis [36]. Moreover, existing study reveals that sesamin could promote osteogenesis by upregulating the Wnt/ β-catenin pathway and inhibit osteoclastogenesis by downregulating the NF-κB pathway, suggesting that it could be a therapeutic medication for osteoporosis treatment [37]. As a major phytosterol in plants, beta-sitosterol has medical benefit of bone strengthening, which was reported to exert protective function on GIOP in rats via the RANKL/OPG pathway [38].…”

Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways

“…The mice OP was induced by ovariectomy (OVX) surgery. Briefly, the OVX was conducted by spaying the bilateral ovaries as mentioned previously [ 11 ]. The sham surgery was performed by repeating the same procedure except for ovary removing.…”

“…Icaritin also promoted new bone formation by activating cAMP signal pathway in osteoblasts [ 9 , 10 ]. In our previous studies, we discovered that sesamin was a potential drug candidate for OP treatment [ 11 ]. However, the treatment effect of sesamin on osteoporotic fracture healing has not been well studied yet.…”

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

“…Moreover, Ses blocked protein expression of glycogen synthase kinase 3 beta (GSK3β), enhancing the wingless-related integration site (Wnt)/β-catenin signaling pathway to increase osteoblast proliferation [ 101 ]. Zhengmeng Yang et al also discovered the anti-osteoclastogenesis effect of Ses to be mediated by NF-κB pathway inhibition, which reduces the expression of CTSK and tartaric-acid phosphatase (TRAP) in osteoclasts [ 102 ]. Moreover, healing of osteoporotic fractures in C57BL/6 mice following OVX surgery was improved by oral administration of Ses [ 103 ].…”