Presence Of Cartilage Oligomeric Matrix Protein Research Articles

Potential role of cartilage oligomeric matrix protein in the modulation of pulmonary arterial smooth muscle superoxide by hypoxia.

Changes in reactive oxygen species and extracellular matrix seem to participate in pulmonary hypertension development. Because we recently reported evidence for chronic hypoxia decreasing expression of cartilage oligomeric matrix protein (COMP) and evidence for this controlling loss of pulmonary arterial smooth muscle bone morphogenetic protein receptor-2 (BMPR2) and contractile phenotype proteins, we examined if changes in superoxide metabolism could be an important factor in a bovine pulmonary artery (BPA), organoid cultured under hypoxia for 48 h model. Hypoxia (3% O2) caused a depletion of COMP in BPA, but not in bovine coronary arteries. Knockdown of COMP by small-interfering RNA (siRNA) increased BPA levels of mitochondrial and extra-mitochondrial superoxide detected by MitoSOX and dihydroethidium (DHE) HPLC products. COMP siRNA-treated BPA showed reduced levels of SOD2 and SOD3 and increased levels of NADPH oxidases NOX2 and NOX4. Hypoxia increased BPA levels of MitoSOX-detected superoxide and caused changes in NOX2 and SOD2 expression similar to COMP siRNA, and exogenous COMP (0.5 μM) prevented the effects of hypoxia. In the presence of COMP, BMPR2 siRNA-treated BPA showed increases in superoxide detected by MitoSOX and depletion of SOD2. Superoxide scavengers (0.5 μM TEMPO or mitoTEMPO) maintained the expression of contractile phenotype proteins calponin and SM22α decreased by 48 h hypoxia (1% O2). Adenoviral delivery of BMPR2 to rat pulmonary artery smooth muscle cells prevented the depletion of calponin and SM22α by COMP siRNA. Thus, COMP regulation of BMPR2 appears to have an important role in controlling hypoxia-elicited changes in BPA superoxide and its potential regulation of contractile phenotype proteins.

Effect of circadian rhythm, age, training and acute lameness on serum concentrations of cartilage oligomeric matrix protein (COMP) neo-epitope in horses.

SummaryBackgroundMolecular serum markers that can identify early reversible osteoarthritis (OA) in horses are lacking.ObjectivesWe studied serum concentrations of a novel cartilage oligomeric matrix protein (COMP) neo‐epitope in horses subjected to short‐term exercise and with acute lameness. The effects of circadian rhythm and age were also evaluated.Study designLongitudinal studies in healthy horses and cross‐sectional comparison of lame and non‐lame horses.MethodsSera were collected from five horses before and after short‐term interval exercise and during full‐day box rest. Sera from 32 acutely lame horses were used to evaluate age‐related effects. Independent samples from control horses (n = 41) and horses with acute lameness (n = 71) were included. COMP neo‐epitope concentrations were analysed using custom‐developed inhibition ELISAs validated for equine serum. The presence of COMP neo‐epitope was delineated in healthy and osteoarthritic articular cartilage with immunohistochemistry.Results COMP neo‐epitope concentrations decreased after speed training but returned to baseline levels post‐exercise. No correlations between age and serum COMP neo‐epitope concentrations were found (r = 0.0013). The mean (±s.d.) serum concentration of COMP neo‐epitope in independent samples from non‐lame horses was 0.84 ± 0.38 μg/mL, and for lame horses was 5.24 ± 1.83 μg/mL (P<0.001). Antibodies against COMP neo‐epitope did not stain normal articular cartilage, but intracytoplasmic staining was found in superficial chondrocytes of mild OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage.Main limitations ELISA was based on polyclonal antisera rather than a monoclonal antibody. There is a sex and breed bias within the groups of horses, also it could have been of value to include horses with septic arthritis and tendonitis and investigated joint differences.ConclusionsThis COMP neo‐epitope can be measured in sera, and results indicate that it could be a biomarker for pathologic fragmentation of cartilage in connection with acute joint lameness.

Endothelin‐1 and COMP Regulate Heme Biosynthesis and Guanylate Cyclase Expression in Smooth Muscle of Pulmonary Arteries

The objective of this study is to examine if heme biosynthesis is regulated in smooth muscle of pulmonary arteries by endothelin‐1 (ET1) and/or conditions modulating the availability of Cartilage Oligomeric Matrix Protein (COMP). Our recent studies in endothelium‐rubbed bovine pulmonary arteries (BPA) organoid cultured for up to 48 hours observed ET1 (10nM) increases superoxide in the mitochondrial matrix and extra mitochondrial regions associated with COMP depletion. While incubation with COMP (0.5μM) attenuated ET1‐induced superoxide increases. We hypothesize that increased superoxide in the mitochondrial matrix could impair heme biosynthesis from protoporphyrin IX (PpIX) by decreasing the availability of Fe2+ and/or ferrochelatase (FECH). To examine this hypothesis, we studied the effects of ET1, COMP and siRNA depletion of COMP on the expression of FECH, transferrin receptor‐1 (TfR1, an indicator of iron availability) and soluble guanylate cyclase (sGC, a key heme‐dependent protein), and on measurements of PpIX (HPLC) and heme content. ET1 decreased FECH, heme and sGC, and increased PpIX and TfR1. COMP reversed these effects of ET1, and COMP also decreased PpIX and increased heme in the absence of ET1. The depletion of COMP by siRNA increased detection of mitochondrial Matrix (MitoSOX‐HPLC) and extramitochondrial (DHE‐HPLC) superoxide, PpIX and TfR1 expression, and decreased the expression of FECH, sGC and the phosphorylation of VASP on the site mediated by cGMP protein kinase. In vascular reactivity studies, it was observed that relaxation of BPA to the nitric oxide donor spermine NONOate was inhibited by organoid culture with ET1, and this effect of ET1 was attenuated in the presence of COMP during the exposure to ET1. Collectively, ET1 and COMP depletion appears to impair the biosynthesis of heme in pulmonary arteries potentially associated with the loss of protective sGC and cGMP vasodilator and remodeling‐inhibitory mechanisms.Support or Funding InformationSupported by NIH Grants HL115124 &amp; HL129797; The Natural Science Foundation of the P. R. China (31400989); The Natural Science Foundation of Heilongjiang Province (C2015069) ; Postdoctoral Science Foundation of Heilongjiang Province (LBHQ15087)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cartilage oligomeric matrix protein-induced complement activation in systemic sclerosis

IntroductionComplexes between cartilage oligomeric matrix protein (COMP) and the complement activation product C3b have been found in the circulation of patients with rheumatoid arthritis and systemic lupus erythematosus. In systemic sclerosis (SSc) COMP expression in the skin is upregulated both in lesional and non-lesional skin, which is also reflected in an increased amount of circulating COMP. We investigated the presence of COMP-C3b complexes in serum and skin biopsies of patients with SSc.MethodsThe presence of COMP and COMP-C3b complexes in the serum of 80 patients with limited cutaneous SSc (lcSSc, n = 40) and diffuse cutaneous SSc (dcSSc, n = 40) and 97 healthy controls was measured by ELISA and correlated to different clinical parameters. Samples were collected both at baseline and after three to five years to assess longitudinal changes in COMP-C3b complex levels. Furthermore, skin biopsies from seven patients with dcSSc and three healthy controls were analyzed for expression of COMP and deposition of C3b and IgG.ResultsSerum levels of COMP-C3b were found to be elevated in both dcSSc and lcSSc compared to healthy controls and decreased at the second measurement in patients on immunosuppressive therapy. No co-localization of COMP and C3b was found in the skin biopsies, indicating that the COMP-C3b complexes are formed upon release of COMP into the circulation.ConclusionCOMP-C3b complexes are found in the serum of patients with SSc. The lack of co-localization between COMP and C3b in the skin suggests that COMP does not drive complement activation in the skin in SSc.

COMP: a candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker

Objective:Cartilage oligomeric matrix protein (COMP), primarily found in cartilage, is thought to be an important regulator of assembly and maintenance of the fibrillar collagen I and II networks. Recently, COMP...

COMP Acts as a Catalyst in Collagen Fibrillogenesis

We have previously reported that COMP (cartilage oligomeric matrix protein) is prominent in cartilage but is also present in tendon and binds to collagens I and II with high affinity. Here we show that COMP influences the fibril formation of these collagens. Fibril formation in the presence of pentameric COMP was much faster, and the amount of collagen in fibrillar form was markedly increased. Monomeric COMP, lacking the N-terminal coiled-coil linker domain, decelerated fibrillogenesis. The data show that stimulation of collagen fibrillogenesis depends on the pentameric nature of COMP and not only on collagen binding. COMP interacts primarily with free collagen I and II molecules, bringing several molecules to close proximity, apparently promoting further assembly. These assemblies further join in discrete steps to a narrow distribution of completed fibril diameters of 149 +/- 16 nm with a banding pattern of 67 nm. COMP is not found associated with the mature fibril and dissociates from the collagen molecules or their early assemblies. However, a few COMP molecules are found bound to more loosely associated molecules at the tip/end of the growing fibril. Thus, COMP appears to catalyze the fibril formation by promoting early association of collagen molecules leading to increased rate of fibrillogenesis and more distinct organization of the fibrils.