Magnolol prevents ovariectomy­induced bone loss by suppressing osteoclastogenesis via inhibition of the nuclear factor­κB and mitogen­activated protein kinase pathways.

Magnolol is the active component of the traditional Chinese medicine Magnolia officinalis, and has antioxidant, anti­inflammatory and anticancer activities, as well as an effect on bone metabolism in vitro. In the present study, it is reported that magnolol suppresses osteoclastogenesis in vivo and in vitro. Magnolol prevented ovariectomy­induced bone loss and osteoclastogenesis in vivo, and decreased the serum levels of C­terminal telopeptide of type 1 collagen, interleukin­6, tumor necrosis factor (TNF)­α and tartrate­resistant acid phosphatase 5B. In vitro, magnolol inhibited the osteoclastogenesis induced by the receptor activator for nuclear factor­κB ligand, and impaired the osteoclast function in bone marrow monocytes and RAW264.7 cells in a dose­dependent manner. Furthermore, magnolol suppressed the expression levels of the osteoclastogenesis markers cathepsin K, calcitonin receptor, matrix metalloproteinase 9, TNF receptor­associated factor 6 and tartrate­resistant acid phosphatase by inhibiting the nuclear factor­κB and mitogen­activated protein kinase pathways. Therefore, magnolol is a promising agent for the treatment of osteoporosis and associated disorders.

[Expression and regulation of the SOST gene].

Sclerostin(SOST), mainly expressed in osteocytes, is a negative regulator of bone formation. Hormones PTH and E2 inhibit the expression of the SOST gene. Transcription factors Osterix, Runx2, and Mef2c promote the SOST expression, while Sirt1 negatively regulates the SOST expression. In addition, the expression of the SOST gene is regulated by epigenetic mechanisms, such as DNA methylation and microRNA. Mutations in the SOST gene, which cause sclerosteosis and Van Buchem diseases, are associated with osteoporosis. Wnt and BMP are two important signaling pathways in bone metabolic regulation. SOST can regulate osteoblastic differentiation and bone formation by binding type I/II receptors and co-receptor LRP5/6 to inhibit BMP and Wnt signaling pathways. Suppression of SOST provides a new approach for osteoporosis treatment. This review covers the structure, function and expression regulation of the SOST gene, human disease association, mechanism in the regulation of bone metabolism and prospect in clinical application.