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

• Published in: Nutrients Vol. 13; no. 12; p. 4455
• Main Authors: Yang, Zhengmeng, Feng, Lu, Wang, Haixing, Li, Yucong, Lo, Jessica Hiu Tung, Zhang, Xiaoting, Lu, Xuan, Wang, Yaofeng, Lin, Sien, Tortorella, Micky D, Li, Gang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.12.2021; MDPI
• Subjects: Animals; beta Catenin - metabolism; Bioactive compounds; Biological activity; Biomedical materials; Bone growth; Bone loss; Bone resorption; Bone Resorption - metabolism; Cell Differentiation - drug effects; Dioxoles - pharmacology; Female; HEK293 Cells; Humans; Kinases; Lignans - pharmacology; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; NF-κB; NF-κB protein; Osteoblasts - drug effects; Osteoclastogenesis; Osteoclasts - drug effects; Osteogenesis; Osteogenesis - drug effects; Osteoporosis; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - metabolism; Ovariectomy; Phosphorylation; Post-menopause; Proteins; RANK Ligand - metabolism; RAW 264.7 Cells; Regulation; RNA, Long Noncoding - metabolism; sesamin; Tumor necrosis factor-TNF; Wnt protein; Wnt Signaling Pathway - drug effects; Wnt/β-catenin; β-Catenin; NF-κB; Wnt/β-catenin; sesamin; osteogenesis; DANCR; osteoclastogenesis; osteoporosis
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13124455

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.