A gene expression study of normal and damaged cartilage in anteromedial gonarthrosis, a phenotype of osteoarthritis

Abstract

SummaryObjectiveTo identify osteoarthritis (OA) relevant genes and pathways in damaged and undamaged cartilage isolated from the knees of patients with anteromedial gonarthrosis (AMG) – a specific form of knee OA.DesignCartilage was obtained from nine patients undergoing unicompartmental knee replacement (UKR) for AMG. AMG provides a spatial representation of OA progression; showing a reproducible and histologically validated pattern of cartilage destruction such that damaged and undamaged cartilage from within the same knee can be consistently isolated and examined. Gene expression was analysed by microarray and validated using real-time PCR.ResultsDamaged and undamaged cartilage showed distinct gene expression profiles. 754 genes showed significant up- or down-regulation (non-False discovery rate (FDR) P < 0.05) with enrichment for genes involved in cell signalling, Extracellular Matrix (ECM) and inflammatory response. A number of genes previously unreported in OA showed strongly altered expression including RARRES3, ADAMTSL2 and DUSP10. Confirmation of genes previously identified as modulated in OA was also obtained e.g., SFRP3, MMP3 and IGF1.ConclusionsThis is the first study to examine a common and consistent phenotype of OA to allow direct comparison of damaged and undamaged cartilage from within the same joint compartment. We have identified specific gene expression profiles in damaged and undamaged cartilage and have determined relevant genes and pathways in OA progression. Importantly this work also highlights the necessity for phenotypic and microanatomical characterization of cartilage in future studies of OA pathogenesis and therapeutic development.

ADAMTS and ADAM metalloproteinases in osteoarthritis – looking beyond the ‘usual suspects’

“…ADAM12 is the ADAM most consistently reported to display increased expression in human OA cartilage10, 11, 12, 15, 16, 17, 62. Its expression is reported to correlate with Mankin score 62 , and increased expression has also been reported in mice 2 weeks after DMM surgery 7 .…”

Intrauterine low‐functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring

“…In the present study, we demonstrated the negative effect of PNE on IGF1 signaling and matrix genes expression. Due to the critical role of IGF1 signaling in promoting proteoglycan and collagen network formation, and thereby improving mechanical properties, a reduction of IGF1 signaling was associated with OA progression (35, 36). It is possible that reduced IGF1 signaling mediate the toxic effect of PNE on cartilage development.…”

Models to define the stages of articular cartilage degradation in osteoarthritis development

“…Indeed, comparison between damaged and undamaged areas of the condyle, as described in (Snelling et al . ), shows expression patterns of genes involved in cell signalling, extracellular matrix remodelling and inflammatory responses; these include matrix metalloproteinases (MMPs), growth factor signalling proteins, collagens and SOX 9, amongst other common OA genes (Sato et al . ; Geyer et al .…”

“…The use of such protocols has identified various pathways and molecular markers for early and late OA. Indeed, comparison between damaged and undamaged areas of the condyle, as described in (Snelling et al 2014), shows expression patterns of genes involved in cell signalling, extracellular matrix remodelling and inflammatory responses; these include matrix metalloproteinases (MMPs), growth factor signalling proteins, collagens and SOX 9, amongst other common OA genes (Sato et al 2006;Geyer et al 2009). Fukui et al (2008) have separated the severity of degradation by grouping the samples (from the same OA patients' joint) into four distinct areas depending on the zones of the articular cartilage affected (preserved area, damaged with superficial, middle and deep zones present, damaged with middle and deep zones, damaged with deep zones only).…”