Correlation Analysisof Gene Expression Profiles Between B Cells And Monocytes And Identification Of Gene Networks For BMD

As the population of the world grows and ages, osteoporosis has become one of the most serious public health problems in worldwide. Bone mineral density (BMD) is a major risk factor for osteoporosis and has widely be used as surrogate for searching genes underlying osteporosis. Evidence for genetic determination of BMD has been gleaned from many family ad twin studies, which suggested that60-90%of BMD variation is attributed to genetic components.However, the majority of genetic component for BMD variation still remain to be identified.B cell and monocyte may be two closely related types of cells. Previous studies found that they were both immune cells, produced in bone marrow, and playing important roles in bone metabolism. In order to systemic search the relationship between circulating monocyte and B cell at the gene expression level,1)we performed a correlation study between them based on a whole genome gene expression data set.2) we seach gene modules associated with BMD and explore the biological importance of them.Correlation study with a Caucasian sample include76subjects with extremely low (n=40) and high (n=36) BMD. Circulating monocyte and B cell were extracted from peripheral venous blood and Affymetrix HG-U133A GeneChip(?) arrays were used to test the gene expression. Affymetrix Microarray Suite5.0(Affymetrix) default settings were used to generate array raw data in CEL files, quantify expression and to normalize the initial results for all target probe sets, the correlation analysis were carried out based on the1107Osteoporosis related genes selected from4279genes significant expressed in B cell and monocyte.Significant positive correlation relationship(R=0.900,P<0.01) was observed for the whole dataset, at the same time, significant positive correlation was observed either for all samples in the genome level or for251out of1107genes at study group level. At pathway level, we conducted correlation analysis for2well-known Osteoporosis-related pathways RANKL/RANK OPG and Wnt/β-catenin signaling, Pearson’s correlation coefficient are0.918and0.508seperately.In a word.positive correlation relationship between B cell and monocyte been found either at gene or pathway level, which indicate that these two cell types share similar expression profile pattern in their ways function in bone metabolisms,and there may be a potential functional co-express mechanism between B cell and monocyte, which affects the bone metabolism.In WGCNA study, Circulating B cell were extracted from peripheral venous blood from Caucasian sample include79subjects with extremely low (n=39) and high (n=40) BMD. Circulating Monocyte were extracted from peripheral venous blood from Caucasian sample include80subjects with extremely low (n=40) and high (n=40) BMD. Gene expression were tested with Affymetrix HG-U133A GeneChip(?) arrays.Followed by MAS5.0software to generate array raw data. Weighted gene coexpression network analysis (WGCNA) was used for network construction, Index Gene Significance was used for qualify the relationship between networks and BMD.10networks were constructed with B cell expression profiles,but there is no significance assocation between either of the networks and BMD.Meanwhile,7networks were constructed with monocyte expression profile,module blue and brown were proved to be associated with BMD,and the relationship was supported by BMD related GWAS study. Functional annotation of by Gene Ontology indicates biological processes such as cellular protein metabolic process,RNA metabolic process and RNA processing are significantly overrepresented in module brown,while translation, cellular protein metabolic process and protein metabolic process are significantly overrepresented in module blue.Results suggest above biological process may affects bone metabolism,futher researches focus on gene fuctional for genes in module blue and brown and corresponding GO process will be helpful for understanding their mechanisms in osteoporosis.For the first time, our study explored and found that there is positive correlation relationship between expression profile of B cell and monocyte,which suggest there may be co-express mechanism between B cell and monocyte, which affects the bone metabolism, what’s more, we have used transcriptional network analysis to elucidate modules that appear to play an important role in the regulation of bone mass with microarray expression data on monocytes and B cell isolcated from Caucasians. The study improved our knowledge of BMD and will benefit for future similar studies.