Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric matrix protein levels.
ABSTRACT Extensive joint hypermobility, lower serum cartilage oligomeric matrix protein (COMP) levels, and early-onset osteoarthritis (OA) are phenotypes of inherited pseudoachondroplasia and multiple epiphyseal dysplasia. However, few studies have evaluated the association between articular hypermobility and primary OA. We undertook the present study to evaluate this association and to test the hypothesis that COMP levels are associated with hypermobility in patients with OA and individuals without OA.
Two separate cohorts were available for analysis, the CARRIAGE (CARolinas Region Interaction of Aging Genes and Environment) extended family and a subset of the GOGO (Genetics of Generalized Osteoarthritis) sibpair cohort. In the CARRIAGE family, we performed hand and knee examinations and hypermobility evaluations (Beighton criteria) and obtained sera for measurement of COMP and hyaluronan (HA). Data on COMP and HA levels and extensive joint radiographic and hypermobility data were also available for the GOGO cohort.
The prevalence of hypermobility was 13% in the CARRIAGE family and 5% in the GOGO cohort. In the CARRIAGE family, hypermobility was associated with a significantly reduced prevalence of hand (especially proximal interphalangeal joint) and knee OA and lower mean serum COMP levels, both in the total cohort and in non-hand-OA subgroups. These results were further validated in the GOGO subsets without radiographic OA, in which hypermobility was also associated with a significantly reduced mean serum COMP level (P < 0.0001 adjusted for age). Serum HA levels did not differ in relation to hypermobility in either cohort.
The present results indicate that there is an inverse relationship between hypermobility and hand and knee OA, and that hypermobility is associated with lower serum COMP levels. Genetic variations of the COMP gene may account for some subgroups of benign joint hypermobility.
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a progressive and life threatening disease with median survival of 2.5-3 years. The IPF lung is characterized by abnormal lung remodeling, epithelial cell hyperplasia, myofibroblast foci formation, and extracellular matrix deposition. Analysis of gene expression microarray data revealed that cartilage oligomeric matrix protein (COMP), a non-collagenous extracellular matrix protein is among the most significantly up-regulated genes (Fold change 13, p-value <0.05) in IPF lungs. This finding was confirmed at the mRNA level by nCounter® expression analysis in additional 115 IPF lungs and 154 control lungs as well as at the protein level by western blot analysis. Immunohistochemical analysis revealed that COMP was expressed in dense fibrotic regions of IPF lungs and co-localized with vimentin and around pSMAD3 expressing cells. Stimulation of normal human lung fibroblasts with TGF-β1 induced an increase in COMP mRNA and protein expression. Silencing COMP in normal human lung fibroblasts significantly inhibited cell proliferation and negatively impacted the effects of TGF-β1 on COL1A1 and PAI1. COMP protein concentration measured by ELISA assay was significantly increased in serum of IPF patients compared to controls. Analysis of serum COMP concentrations in 23 patients who had prospective blood draws revealed that COMP levels increased in a time dependent fashion and correlated with declines in force vital capacity (FVC). Taken together, our results should encourage more research into the potential use of COMP as a biomarker for disease activity and TGF-β1 activity in patients with IPF. Hence, studies that explore modalities that affect COMP expression, alleviate extracellular matrix rigidity and lung restriction in IPF and interfere with the amplification of TGF-β1 signaling should be persuaded.PLoS ONE 01/2013; 8(12):e83120. · 3.73 Impact Factor
Article: Epidemiology of osteoarthritis.[show abstract] [hide abstract]
ABSTRACT: Osteoarthritis (OA) is the most common form of arthritis in the United States and is a leading cause of disability. It is typically defined in epidemiologic studies by radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include numerous person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. In studying OA, several methodologic challenges exist that can hamper our ability to identify pertinent relationships.Rheumatic diseases clinics of North America 02/2013; 39(1):1-19. · 2.59 Impact Factor
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ABSTRACT: Abstract Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell-matrix interactions. Recent studies have shown that genetic variation is a significant risk factor for Achilles tendinopathy, and the genes encoding cartilage oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as good candidate genes for association with Achilles tendinopathy. This study aimed to test the association of sequence variants within these candidate genes with the risk of Achilles tendinopathy in participants from South Africa (SA) and Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants clinically diagnosed with Achilles tendinopathy were genotyped for five single nucleotide polymorphisms within the COMP and THBS2 genes in this case-control study. There was no difference in genotype distributions between control and tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS populations. As the selection of COMP and THBS2 as candidate genes was hypothesis driven, based on biological function, the possibility that other variants within these genes are associated with Achilles tendinopathy cannot be excluded.Journal of Sports Sciences 07/2013; · 2.08 Impact Factor