Tomatidine Attenuates Estrogen Deficiency-induced Bone Mass Loss By Modulating Osteoclast Differentiation

With the aggravation of social aging,the incidence of osteoporosis is increasing,which has become one of the chronic diseases that seriously affect the health of the elderly population.The complications caused by bone mass loss and bone micro structure destruction,such as pain,physical deformity,and brittle fracture,have caused huge social and economic burden,which is an urgent problem to be solved.Previous studies have shown that bone metabolism is a dynamic equilibrium process in which osteoblasts and osteoclasts play an important role.In perimenopause and 10 years after menopause,bone metabolism was in a state of high turnover,entering the elderly,osteoblast and osteoclast activity were decreased,and bone metabolism was mainly low turnmover type.Osteoclasts,as the only cells with bone resorption function in vivo,their activity is relatively increased after estrogen withdrawal,which is closely related to the occurrence of osteoporosis.Therefore,anti-bone resorption drugs are the first-line regimen for the treatment of osteoporosis.Perimenopause and postmenopausal osteoporosis 1s characterized by reduced estrogen levels,and estrogen deficiency leads to a range of pro-inflammatory factors such as interleukm-2(IL-2),IL-1? IL-6,and tumor necrosis factor-a(tumor necrosis factor,The production of TNF-? and prostaglandin E2(PGE2)increased.Pro-inflammatory factor can promote the differentiation of osteoclasts,so that bone metabolism is unbalanced and bone mass loss is aceelerated.Tomatidine is a steroid alkaloid derived from Solanaceae,which has a certain anti-inflammatory effect,but its role and mechanism in osteoclast differentiation and estrogen deficiency induced osteoporosis is not clear.Therefore,the purpose of this study was to explore the effect of tomatidine on osteoclast differentiation and to provide a potential new scheme for the prevention and treatment of postmenopausal osteoporosis.In this study,the anti-inflammatory activity of tomatidine was evaluated in vitro,its role in osteoclast differentiation was clarified,and the specific signaling pathway regulation mechanism was explored.In vivo,the ovariectomy model of mice was established to verify the therapeutic effect of ovariectomy on osteoporosis caused by estrogen deficiency.This study is divided into the following three parts:(1)The effect of Tomatidine on inflammatory response induced by IL-1? and lipopolysaccharide in vitro;(2)The effect of Tomatidine on osteoclast differentiation and its regulation mechanism;(3)The physiological effect of Tomatidine on cancellous bone mass of C57BL/6 mice after ovariectomy.