A whole-genome transcriptome analysis of articular chondrocytes in secondary osteoarthritis of the hip

Abstract

ObjectiveTo date, exhaustive gene expression analyses of chondrocytes in hip osteoarthritis (OA) have yielded specific gene expression patterns. No study has reported on the exhaustive transcriptome of secondary hip OA based on acetabular dysplasia in a Japanese population, while previous reports have focused on primary or idiopathic hip OA in Caucasian populations. This study aims to search for specific gene expression patterns of secondary hip OA chondrocytes by transcriptome analysis.DesignHuman articular cartilage was obtained from femoral heads following hemiarthroplasty for femoral neck fracture (N = 8; non-OA) and total hip arthroplasty for secondary hip OA (N = 12). Total RNA was extracted from the articular cartilage and submitted for microarray analysis. The obtained data were used to perform gene expression analysis, GO enrichment analysis and pathway analysis and were compared with data from primary hip OA in Caucasian populations in the literature.ResultsWe identified 888 upregulated (fold change: FC ≥ 2) and 732 downregulated (FC ≤ 0.5) genes in hip OA versus non-OA chondrocytes, respectively. Only 10% of upregulated genes were common between the secondary and primary OA. The newly found genes prominently overexpressed in the secondary hip OA chondrocytes were DPT, IGFBP7, and KLF2. Pathway analysis revealed extracellular matrix (ECM)-receptor interaction as an OA-related pathway, which was similar to previous reports in primary hip OA.ConclusionsThis is the first study to report the genome-wide transcriptome of secondary hip OA chondrocytes and demonstrates new potential OA-related genes. Gene expression patterns were different between secondary and primary hip OA, although the results of pathway and functional analysis were similar.

IGFBP7 acts as a negative regulator of RANKL‐induced osteoclastogenesis and oestrogen deficiency‐induced bone loss

“…Arnold et al reported that IGFBP7 promoted osteogenesis of stem cells and may protect them from bone disease in multiple myeloma . Using protein interaction and microRNA network analyses, Wang et al reported that IGFBP7 expression was associated with the development of osteoarthritis (OA), which was confirmed by two other studies . In our previous study, we reported that IGFBP7 enhanced osteogenic differentiation of BMSCs via the Wnt/β‐catenin signalling pathway in vitro and promoted new bone formation in vivo .…”

“…IGFBP7 is methylated in subchondral bones and is related to its sclerosis . IGFBP7 is also reported to be associated with the development of OA, another bone metabolism‐related orthopaedic disease . As direct evidence, our previous study showed that IGFBP7 enhanced osteogenesis in vitro and in vivo .…”

“…17 Using protein interaction and microRNA network analyses, Wang et al reported that IGFBP7 expression was associated with the development of osteoarthritis (OA), 18 which was confirmed by two other studies. 19,20 In our previous study, we reported that IGFBP7 enhanced osteogenic differentiation of BMSCs via the Wnt/β-catenin signalling pathway in vitro and promoted new bone formation in vivo. 21 However, the function of IGFBP7 in osteoclast differentiation and osteoporosis still remains unclear.…”

Investigating the molecular control of deer antler extract on articular cartilage 

“…Notch3 is a family member of Notch receptors, and genetic deletion of Notch3 or the blockade of Notch3 signaling prevents joint damage and attenuates in ammation of in ammatory arthritis [72]. (a chloride intracellular channel protein) are reported to be highly expressed under osteoarthritic condition [86][87][88][89][90][91][92][93][94][95]. Thus, these results suggest that DAE might serve as a candidate supplement for preventing cartilage degeneration and in ammation.…”

Insights Into the Molecular Mechanism of Deer Antler Extract Serving as a Potential Chondroprotective Agent for Articular Cartilage

“…Ramp3 is a receptor activitymodifying protein that is highly expressed during joint in ammation [83]. Cyp1b1 (a member of the cytochrome P450 enzyme family), Pcsk1n (an inhibitor of prohormone convertase 1), Dlx3 (a family member of homeobox proteins), Nkd2 (a regulator of in ammatory response), Mmp19 (a subtype of matrix metalloproteinases), Htra4 (a subtype of serine proteases), Aplnr (a G protein-coupled receptor of apelin), Tubb2b (a beta isoform of tubulin), Arg1 (a cytosolic manganese-dependent enzyme) and Clic5 (a chloride intracellular channel protein) are reported to be highly expressed under osteoarthritic condition [84][85][86][87][88][89][90][91][92][93]. Thus, these results suggest that DAE play a potential role in preventing articular cartilage degeneration and in ammation by inhibiting multiple genes involved in the pathophysiology of osteoarthritis.…”