An in Vivo Genome Wide Gene Expression Study of Circulating Monocytes Suggested GBP1, STAT1 and CXCL10 As Novel Risk Genes for the Differentiation of Peak Bone Mass

Peak bone mass (PBM) is an important determinant of osteoporosis. Circulating monocytes serve as early progenitors of osteoclasts and produce important molecules for bone metabolism. To search for genes functionally important for PBM variation, we performed a whole genome gene differential expression study of circulating monocytes in human premenopausal subjects with extremely low (N=12) vs. high (N=14) PBM. We used Affymetrix HG-U133 plus2.0 GeneChip arrays. We identified 70 differential expression probe sets (p<0.01) corresponding to 49 unique genes. After false discovery rate adjustment, three genes [STAT1, signal transducer and activator of transcription 1; GBP1, guanylate binding protein 1; CXCL10, Chemokine (C-X-C motif) ligand 10] expressed significantly differentially (p<0.05). The RT-PCR results independently confirmed the significantly differential expression of GBP1 gene, and the differential expression trend of STAT1. Functional analyses suggested that the three genes are associated with the osteoclastogenic processes of proliferation, migration, differentiation, migration, chemotaxis, adhesion. Therefore, we may tentatively hypothesize that the three genes may potentially contribute to differential osteoclastogenesis, which may in the end lead to differential PBM. Our results indicate that the GBP1, STAT1 and CXCL10 may be novel risk genes for the differentiation of PBM at the monocyte stage.