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Altered gene expression in multiple key pathways in MSCs from people with osteoporosis compared to people who do not have osteoporosis

ABSTRACT: Osteoporosis is caused by imbalanced bone remodelling homeostasis and is highly prevalent in post-menopausal women. The impact of osteoporosis on mesenchymal stromal cells (MSCs) is a key area of research as they are the progenitors of osteoblasts and are therefore critical to bone homeostasis. TBioinformatic analysis of transcriptional profiling data revealed specific misregulation of genes involved in the processing and trafficking of cellular components, as well as downregulation of Neo1 which has an important role in controlling cell fate choice. These data indicate that the therapeutic targeting of bone marrow MSCs to increase their numbers, to support the appropriate processing of cellular contents, or to redirect cell fate choice may provide new methods for the treatment of osteoporosis, thereby reducing fracture-associated morbidity and improving quality of life for the 200 million people living with osteoporosis globally.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189524 | GEO | 2024/04/09

REPOSITORIES: GEO

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Project description:Background: Primary osteoporosis has increasingly become one of the risk factors affecting human health, and the clinical effect and action mechanism of traditional Chinese medicine in the treatment of primary osteoporosis have been widely studied. Previous studies have confirmed that in traditional Chinese medicine , Drynaria rhizome has a role in improving bone density. In this study, TMT-based proteomic analysis was conducted to derive potential targets for Drynaria rhizome treatment in postmenopausal osteoporosis. Methods: The model group (OVX) and experimental group (OVXDF) for menopausal osteoporosis were established using the universally acknowledged ovariectomy method, and the latter group received intragastric administration of 8.1 g /kg-1 of Drynaria rhizome for 12 weeks. After 12 weeks, femurs of rats selected for this study were examined with a bone mineral density (BMD) test, Micro-CT, ELISABiochemical testing, hematoxylin and eosin (HE) staining, and immunohistochemistry. A certain portion of the bone tissue was studied with a TMT-based proteomic analysis and functional and pathway enrichment analysis. Finally, key target genes were selected for Western blotting for validation. Results: The comparison of the OVXDF and OVX groups indicated that Drynaria rhizome could improve bone density. In the TMT-based proteomic analysis, the comparison of these two groups revealed a total of 126 differentially expressed proteins (DEPs), of which 62 were upregulated and 64 were downregulated. Further, by comparing the differential genes between the OVXDF and OVX groups and between the OVX and SHAM groups, we concluded that the 27 differential genes were significantly changed in the rats selected for the osteoporosis model after Drynaria rhizome intragastric administration. The gene ontology (GO) enrichment analysis of DEPs showed that molecular function was mainly involved in biological processes, such as glucose metabolism, carbohydrate metabolism, immune responses, and aging. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEPs revealed that multiple differential genes were enriched in the estrogen and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Relationships with nitrogen metabolism, glycerophospholipid metabolism, secretion systems, and tumor diseases were also observed. Western blotting was consistent with the analysis. Conclusions: We used TMT-based proteomics to analyze the positive effects of TCM Drynaria rhizome, which can regulate related proteins through the unique roles of multiple mechanisms, targets, and pathways. This treatment approach can regulate oxidative stress, improve lipid metabolism, reduce the inflammatory response mechanism, and improve bone density. These benefits highlight the unique advantages of TCM in the treatment of primary osteoporosis.

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Altered gene expression in multiple key pathways in MSCs from people with osteoporosis compared to people who do not have osteoporosis

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