Transcriptomic Data Identified Key Transcription Factors for Osteoporosis in Caucasian Women.

Abstract

Osteoporosis is a prevalent bone metabolic disease, mainly caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Identifying the key transcription factors and understanding the regulatory network influencing osteoclastogenesis will be helpful to explore the potential biological mechanism for osteoporosis. In our study, peripheral blood monocyte (PBM) was used as a cell model for bone mineral density (BMD) research. PBMs serve as progenitors of osteoclasts and produce important cytokines for osteoclastogenesis. In our study, via exon arrays, gene expression profiles of PBMs were analyzed between high versus low hip BMD groups. Transcription factors for differentially expressed genes were then predicted based on the enrichment analysis. We found that 591 genes were differentially expressed between the two BMD groups (nominally significant, raw p value < 0.05). For high BMD subjects, 482 genes were up-regulated and 109 genes were down-regulated. We then found 29 potential transcription factors for up-regulated genes and nine transcription factors for down-regulated genes. Among these transcription factors, HMGA1 and NFKB2 were differentially expressed between high versus low BMD groups. In addition, their regulation types with their target genes were consistent with the information from public databases. Our findings of key transcription factors and their target genes for osteoporosis were further validated by GWAS analysis. Overall, we predicted important transcription factors for osteoporosis. We were also able to infer the regulatory mechanism that exists between transcription factors and target genes in bone metabolism.