Journal
OSTEOARTHRITIS AND CARTILAGE
Volume 22, Issue 12, Pages 2017-2024Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2014.07.024
Keywords
Osteoarthritis; Genetics; Functional genomics; Transcriptomics; Epigenetics; microRNAs
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Recent developments in genetics/genomics of osteoarthritis (OA) are discussed to improve our understanding of OA pathophysiology. The discovery of a novel variant near the NCOA3 (nuclear receptor coactivator 3) gene associated with hip OA and the regulation of GDF5 gene by four transcription factors via the OA susceptibility locus rs143383 are among important findings in OA genetics. Several microarray-based gene expression studies were published for different tissues of the joint. In OA synovium elevation of collagens and cross-linking enzymes (COL1A1, COL5A1, PLOD2, LOX and TIMP1) responsive to TGF-beta was found as well as differential expression pattern between different areas of the osteoarthritic synovial membrane. In OA peripheral blood the role of apoptotic genes was highlighted, while whole genome expression profiling in OA subchondral bone and cartilage revealed common genes in cartilage and bone to be involved in OA development. In epigenetics, several microRNAs (miRNAs) were found to regulate genes' expression in chondrocytes, among which miR-125, miR-127b miR-21, miR-148a and their use as potential drug targets was highlighted. Future studies must focus on the integration of genetics, genomics and epigenetics for the identification of signaling pathways and regulatory networks responsible for OA development. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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