Solanum nigrum Line inhibits osteoclast differentiation and suppresses bone mineral density reduction in the ovariectomy‑induced osteoporosis model

Abstract

Bone homeostasis is maintained by osteoclasts that absorb bone and osteoblasts that form bone tissue. Menopausal osteoporosis is a disease associated with aging and hormonal changes due to menopause causing abnormal activation of osteoclasts, resulting in a decrease in bone density. existing treatments for osteoporosis have been reported to have serious side effects, such as jawbone necrosis and breast and uterine cancer; therefore, their use by patients is decreasing, whilst studies focusing on alternative treatments are increasingly popular. Solanum nigrum line (Sl) has been used as a medicinal plant that possesses several pharmacological effects, such as anti-inflammatory and hepatotoxic protective effects. To the best of our knowledge, however, its effects on osteoporosis and osteoclasts have not been demonstrated previously. in the present study, the anti-osteoporotic effect of Sl was investigated using a postmenopausal model of osteoporosis in which Sprague-dawley rat ovaries were extracted. in addition, the inhibitory effects on osteoclast differentiation and function of SL was confirmed using an osteoclast model treated with receptor activator of nF-κB ligand (ranKl) on murine raW 264.7 macrophages. In vivo experiments showed that Sl reduced the decrease in bone mineral density and improved changes in the morphological index of bone microstructure, such as trabecular number and separation. in addition, the number of tartrate resistant acid phosphatase-positive cells in the femur and the expression levels of nuclear factor of activated T-cells cytoplasmic 1 (nFaTc1) and cathepsin K protein were inhibited. In vitro, Sl suppressed ranKl-induced osteoclast differentiation and bone resorption ability; this was mediated by nFaTc1/c-Fos, a key transcription factor involved in osteoclast differentiation, ultimately inhibiting expression of various osteoclast-associated genes. These experimental results show that Sl may be an alternative treatment for osteoporosis caused by abnormal activation of osteoclasts in the future.