Identification of differentially expressed genes in trabecular bone from the iliac crest of osteoarthritic patients

Objective: Osteoarthritis (OA) is clinically characterized by degeneration of the joints and has been traditionally considered a primary disorder of articular cartilage, with secondary changes in the subchondral bone. The increased bone mass and generalized changes in bone quality observed in osteoarthritic patients suggest that OA may be a primary systemic bone disorder with secondary articular cartilage damage. The iliac crest is a skeletal site distant from the affected joint, with a minimal load-bearing function. To provide evidence that OA is a systemic disorder, we searched for differentially expressed genes in the iliac crest bone of patients suffering from hip CA. Material and methods: Gene expression levels between bone samples collected at surgery from the iliac crest of patients undergoing total hip arthroplasty for primary CA and younger donors, who were undergoing spinal arthrodesis, were investigated by means of oligonucleotide microarrays. To verify data detected by microarrays technology, Real Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assays were performed with specimens from osteoarthritic patients and donors, as well as from elderly donors who were undergoing arthroplasty for subcapital femoral neck fracture. Results: The microarray analysis surveyed 8327 genes and identified 83 whose expression levels differed at least 1.5-fold in the OA group (P < 0.005). Comparisons between Real Time RT-PCR data from CA and the two donor groups indicated differential expression of genes involved in bone cell functions in the group of CA patients. The genes identified, including CCL2, FOS, PRSS11, DVL2, AKT1, CA2, BMP6, OMD, MMP2, TGFBR3, FLT1, BMP1 and TNFRS11B, have known roles in osteoblast or osteoclast activities. Conclusions: The data from this study identify a set of genes, closely related to bone cell functions, in which differential regulation in osteoarthritic bone distant from the diseased subchondral bone might underlie the etiopathogenesis of CA as a generalized bone disease. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.