S.-C. Wu

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.

Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density

Osteoporosis (OP) is a major public health problem, mainly characterized by low bone mineral density (BMD). Circulating monocytes (CMCs) may serve as progenitors of osteoclasts and produce a wide variety of factors important to bone metabolism. However, the specific action mechanism of CMCs in the pathogenesis of OP is far from clear. We performed a comparative protein expression profiling study of CMCs in Chinese premenopausal females with extremely discordant BMD, identified a total of 38 differentially expressed proteins, and confirmed with Western blotting five proteins: ras suppressor protein1 (RSU1), gelsolin (GSN), manganese‐containing superoxide dismutase (SOD2), glutathione peroxidase 1(GPX1), and prolyl 4‐hydroxylase β subunit (P4HB). These proteins might affect CMCs trans‐endothelium, differentiation, and/or downstream osteoclast functions, thus contribute to differential osteoclastogenesis and finally lead to BMD variation. The findings promote our understanding of the role of CMCs in BMD determination, and provide an insight into the pathogenesis of human OP.

Genetic and Environmental Correlations between Bone Geometric Parameters and Body Compositions

The purpose of this study was to determine the genetic and environmental correlations between weight, lean mass and bone geometric parameters (sub-periosteal diameter, W; cross-sectional area, CSA; cortical thickness, CT; section modulus, Z; and buckling ratio, BR) of femoral neck. The sample was composed of 512 Caucasian pedigrees, including 2667 females and 1822 males. Bivariate quantitative genetic analyses were performed to evaluate the genetic (ρG), environmental (ρE) and phenotypic (ρP) correlations between the study traits. Univariate genetic analyses showed that the heritabilities (h2) for bone geometric parameters were significant (P < 0.001) ranging from 0.50 to 0.60. The significant common household effects indicated the common environment shared by household members for W, CSA, CT, Z and BR (P < 0.05), but the magnitude was small compared with heritabilities. ρE, ρG and ρP between bone geometric parameters and weight, lean mass were generally significant. Interestingly, lean mass showed both stronger genetic and environmental correlations with the bone geometric parameters than weight. In addition, according to the magnitude of correlation coefficients, the ρG between body compositions and bone geometric parameters were generally stronger thanρE (except for that between BR and body compositions). These data suggested that the geometric parameters of femoral neck are under strong genetic control. Furthermore, some common genetic and environmental factors are shared by bone geometric parameters and weight, lean mass. The results may help understand the intertwined relationships between bone metabolisms, mechanical loading and body compositions.

IDENTIFICATION OF HIGH-SPIN STATES IN NEUTRON-RICH 88,90,92Kr AND 86Se

Level schemes of even–even neutron-rich 88-92Kr and 86Se have been investigated by measuring triple-γ coincidence data from the spontaneous fission of 252Cf with the Gammasphere detector array. The level scheme of 88Kr has been extended up to 7169 keV state. Several new excited states with new transitions have been identified in 90,92Kr and 86Se. Spins and parities have been assigned to levels in these nuclei by following regional systematics and angular correlation measurements. The level structures of the N = 52, 54, Se, Kr, and Sr isotones are discussed.