Although osteoporosis is one of the most common chronic age-related diseases, there is currently no gold standard for treatment. Evidence suggests resveratrol, a natural polyphenolic compound, may be helpful in the treatment of osteoporosis and other diseases. However, the molecular mechanisms underlying the antiosteoporotic effects of resveratrol remain largely unknown. In the present study, KEGG pathway enrichment analysis of resveratrol-targeted genes identified 33 associated pathways, 12 of which were also involved in osteoporosis. In particular, the MDM2/p53 signaling pathway was identified as a potential key pathway among the shared pathways. In vitro experiments indicated that MDM2-mediated p53 degradation induced osteoblast differentiation, and resveratrol could partially reverse p53-dependent inhibition of osteogenic differentiation. These findings suggest resveratrol may alleviate osteoporosis at least in part by modulating the MDM2/p53 signaling pathway.

Osteoporosis is a metabolic disease affecting 40% of postmenopausal women. It is characterized by decreased bone mass per unit volume and increased risk of fracture. We investigated the molecular mechanism underlying osteoporosis by identifying the genes involved in its development. Osteoporosis-related genes were identified by analyzing RNA microarray data in the GEO database to detect genes differentially expressed in osteoporotic and healthy individuals. Enrichment and protein interaction analyses carried out to identify the hub genes among the deferentially expressed genes revealed TP53 , MAPK1 , CASP3 , CTNNB1 , CCND1 , NOTCH1 , CDK1 , IGF1 , ERBB2 , CYCS to be the top 10 hub genes. In addition, p53 had the highest degree score in the protein-protein interaction network. In vivo and in vitro experiments showed that TP53 gene expression and serum p53 levels were upregulated in osteoporotic patients and a mouse osteoporosis model. The elevated p53 levels were associated with decreases in bone mass, which could be partially reversed by knocking down p53. These findings suggest p53 may play a central role in the development of osteoporosis.

Background: As a common metabolic disorder, osteoporosis is characterized by decreasing bone mass density and increased possibility of fragility fracture. The incidence of senile osteoporosis increases year by year. There is no gold standard of treatment for osteoporosis. Tomatidine is the aglycone derivative of tomatine, having the ability to treat various diseases, including osteoporosis. However, the mechanism by which tomatidine improves osteoporosis has not been fully elucidated. Tomatidine is a potential and promising drug for osteoporosis. Material/Methods: In this study, the KEGG pathways that tomatidine-targeted genes enriched in were obtained using bioinformatics methods. The KEGG pathways involved in osteoporosis that were also associated with tomatidine-targeted genes were selected. After analysis of these pathways, essential genes that may be involved in this biological process were identified and validated experimentally. Results: We found 110 osteoporosis related KEGG pathways and 76 tomatidine-targeted genes-related KEGG pathways were obtained. 39 shared KEGG pathways were identified. The top 5 pathways were: pathway of chronic myeloid leukemia, pathway of B cell receptor signaling, pathway in cancer, bladder cancer pathway, and progesteronemediated oocyte maturation pathway. MAPK1, MAP2K1, MAPK3, RAF1 were involved in all the 5 pathways. The p53 signaling pathway and the MAPK signaling pathway were involved in the 5 KEGG pathways. In vitro experiments showed that downregulating p53 expression could be potentially protective for osteoporosis. Conclusions: Tomatidine can improve osteoporosis, and one of the mechanisms of its action is achieved by modulating p53. Tomatidine may be a promising drug for osteoporosis.