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Differential Gene Expression Pattern in Osteoclast Precursor Cells of Indian Postmenopausal Women with and Without Osteoporosis: A Microarray Based Study

Mehrunnisa M Raje, Suhas T Mhaske, Payel Ghosh, Mohan R Wani and Richa Ashma

Background: Osteoporosis is a multifactorial disease with strong genetic and epigenetic component. In spite of enormous candidate gene association studies, the etiology and molecular mechanism of disease is not fully known. For identification of new markers of osteoporosis which could be vital in diagnosis and prognosis of disease, genome-wide microarray expression approach was employed.
Methods: Osteoclast precursor cells were sorted from circulating monocytes of osteoporotic and nonosteoporotic post menopausal females with similar life-style and year after menopause. Following microarray experimentation, gene enrichment analysis was performed on significant DEGs using Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Top 10 novel genes were further used for construction of protein-protein interaction network using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. To validate microarray gene expression pattern, Real time-PCR was performed.
Results: A total of 269 genes were found to be differentially expressed between disease and normal groups, of which 138 were observed to be up regulated and 131 down regulated. Furthermore, novel LHX1 gene was observed to be up regulated and its interaction with BMP4 protein was observed. Three known genes for osteoclastogenesis (viz., CX3CL1, ACP5 and CSF1) were found to be up- regulated. Similar pattern of gene expression have been obtained using RT-PCR.
Conclusion: Significant enrichment of PI3K-Akt and TGF-ß signaling pathways involving DEGs was found in postmenopausal Asian Indian women. Moreover, up regulated LHX1 gene was discovered as novel gene which may have a role in pathogenesis of osteoporosis and can be used for diagnosis and prognosis along with known osteoporotic markers.