Abstract
Postmenopausal osteoporosis (PMOP), as well as its associated increased risk for fragility fracture, is one of the most disabling consequences of aging in women. This present study aimed to identify candidate genes that involve pathogenesis of PMOP and the therapeutic mechanism of Liuweidihuang (LWDH) pills on PMOP. We integrated microarray datasets of PMOP derived from the Gene Expression Omnibus (GEO) to screen differentially expressed genes (DEGs) between PMOP and normal controls as well as patients with PMOP and patients after treatment of LWDH pills. GO and KEGG enrichment analysis for DEGs were performed. The shared DEGs, associated with both the pathogenesis of PMOP and the therapeutic mechanism of LWDH, were further analyzed by protein-protein interaction (PPI) network. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs obtained by our integrated analysis. Compared with normal controls, 1732 DEGs in PMOP were obtained with p<0.05. According to the qRT-PCR results, expression of ATF2, FBXW7, RDX, and RBBP4 was consistent with that in our integrated analysis, generally. GO and KEGG enrichment analysis showed that those DEGs were significantly enriched in regulation of transcription, DNA-dependent, cytoplasm, protein binding, and MAPK signaling pathway. A total of 58 shared DEGs in PMOP versus normal control and in patients with PMOP versus patients after LWDH treatment were identified, which had opposite expression trend in these two comparisons. In the PPI network, CSNK2A1, ATF2, and FBXW7 were three hub proteins. Three genes including ATF2, FBXW7, and RDX were speculated to be therapeutic targets of LWDH for PMOP based on BATMAN-TCM database. We speculated that three genes of ATF2, FBXW7, and RDX may play crucial roles in both pathogenesis of PMOP and therapeutic mechanism of LWDH on PMOP. Our results may provide clues for the molecular pathogenesis of PMOP and offer new possibilities for treatment of PMOP.
Highlights
Postmenopausal osteoporosis (PMOP) often occurs due to the simultaneous interaction of independent predisposing factors, including aging and continuous calcium loss [1]
We selected gene expression datasets of PMOP on the Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo) which is the largest database of high-throughput gene expression data [15]
Four gene expression microarray datasets (GSE100609, GSE56815, GSE13850, and GSE7429) and a microarray dataset associated with therapeutic mechanism of LWDH on PMOP (GSE57273) were enrolled in our study
Summary
Postmenopausal osteoporosis (PMOP) often occurs due to the simultaneous interaction of independent predisposing factors, including aging and continuous calcium loss [1]. It is estimated that osteoporosis-associated fractures affect one-third of women in their lifetime, which is a public health concern [2]. Both in animal models and in humans that were affected by osteoporosis newly, evidences of the relationship between immune system and bone have been accumulated. Estrogen is a well-known regulator of the immune system and T-cell functions. Bone loss induced by estrogen deficiency in menopause is a BioMed Research International complex effect of a multitude of pathways and cytokines working in a cooperative fashion to regulate osteoclastogenesis and osteoblastogenesis [3,4,5,6]. Wnt family members and Wnt inhibitor molecules were involved in the regulation of differentiation of multipotent mesenchymal stem cells into osteoblasts and adipocytes and in the coordination of the switch toward osteo- or adipogenesis fate within bone marrow[7]
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