BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of ...BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.展开更多
Lipid metabolism disorders commonly occur during menopause.Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats,resulting in obesity.Probiotics exh...Lipid metabolism disorders commonly occur during menopause.Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats,resulting in obesity.Probiotics exhibit anti-obesity properties,and their underlying mechanism has been widely reported.In this study,we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite,controlling body weight,correcting obesity-induced abnormalities,enhancing liver lipid metabolism,and protecting liver function in estrogen-deficient rats.The mechanisms associated with the anti-obesity and anti-dyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified.The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha(ERα)and increasing the level of leptin in abdominal adipose tissue.These changes,combined with the increased butyrate concentration and recovered bile acid structure,helped enhance lipid metabolism.Additionally,CCFM1180 treatment was found to be safer than exogenous estrogen supplementation.Thus,L.plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.展开更多
基金Supported by National Natural Science Foundation of China,No.82072425.
文摘BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.
基金funded by the National Natural Science Foundation of China(31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province。
文摘Lipid metabolism disorders commonly occur during menopause.Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats,resulting in obesity.Probiotics exhibit anti-obesity properties,and their underlying mechanism has been widely reported.In this study,we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite,controlling body weight,correcting obesity-induced abnormalities,enhancing liver lipid metabolism,and protecting liver function in estrogen-deficient rats.The mechanisms associated with the anti-obesity and anti-dyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified.The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha(ERα)and increasing the level of leptin in abdominal adipose tissue.These changes,combined with the increased butyrate concentration and recovered bile acid structure,helped enhance lipid metabolism.Additionally,CCFM1180 treatment was found to be safer than exogenous estrogen supplementation.Thus,L.plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.
