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PubMed1994

Non-collagenous protein screening in the human chondrodysplasias: link proteins, cartilage oligomeric matrix protein (COMP), and fibromodulin.

A gel-electrophoretic screening for link proteins, cartilage oligomeric matrix protein (COMP), and fibromodulin abnormalities was performed in fetuses, newborn infants, and children with various types of chondrodysplasia. Microdissected freeze-dried sections of upper tibial growth cartilage were extracted with 4M guanidinium chloride in the presence of proteolysis inhibitors. After dialysis against 8M urea, the extracts were submitted to stepwise ion-exchange chromatography to separate the large proteoglycans (aggrecans) from the other components. The latter were analyzed by gel electrophoresis, electrotransferred onto nitrocellulose membranes, and reacted with specific antibodies. Control samples from individuals with apparently normal growth were analyzed in the same runs. Two link protein bands with abnormal electrophoretic migration were found in a sporadic case of spondylometaphyseal dysplasia, Kozlowski type. Three link protein bands with the same migration as in the control samples were found in thanatophoric dysplasia, homozygous achondroplasia, achondrogenesis type II, hypochondrogenesis, Goldblatt syndrome, Desbuquois dysplasia, pseudoachondroplasia, and diastrophic dysplasia. In several pathologic cases with normal electrophoretic pattern of the link proteins, small link protein fragments appeared after reduction. The gel electrophoretic pattern of COMP was studied in thanatophoric dysplasia, diastrophic dysplasia, homozygous achondroplasia, fibrochondrogenesis, hypochondrogenesis, Goldblatt syndrome, and Kniest dysplasia. In all these cases the pattern was the same as in the control samples. The main band of fibromodulin had a normal migration rate in fibrochondrogenesis, Desbuquois dysplasia, Kniest dysplasia, and pseudoachondroplasia. It was delayed in diastrophic dysplasia.

Carrier Proteins↗
PubMed2003

Ethnic and sex differences in serum levels of cartilage oligomeric matrix protein: the Johnston County Osteoarthritis Project.

OBJECTIVE: Previous descriptions of potential biomarkers of osteoarthritis (OA) have been limited to Caucasians. In the present study, we examined associations between serum levels of cartilage oligomeric matrix protein (COMP) and ethnicity (African American or Caucasian) and sex in the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. METHODS: All African Americans and a randomly selected sample of Caucasians who had available sera and either no radiographic evidence of knee or hip OA according to the Kellgren/Lawrence (K/L) system (K/L grade 0) or radiographic evidence of knee OA (K/L grade 2 or higher) were included. Serum COMP levels were quantified by sandwich enzyme-linked immunosorbent assay, using monoclonal antibodies 16-F12 and 17-C10. Linear regression models were used to assess relationships between serum levels of natural log-transformed COMP (ln COMP) and ethnicity and sex, controlling for age, height, body mass index (BMI), radiographic OA, and the presence of other symptomatic joints. Radiographic OA was defined in separate models as the presence, severity, and laterality of radiographic knee OA, the co-occurrence of radiographic knee and hip OA, and the number of knees and hips with radiographic OA. RESULTS: The 769 subjects in the study sample had a mean +/- SD age of 62 +/- 10.3 years. Levels of ln COMP were associated with age, BMI, and all definitions of radiographic OA (P = 0.0001), and varied by ethnicity and sex. In adjusted models, ln COMP was higher in African American women than in Caucasian women (P = 0.003) and higher in Caucasian men than Caucasian women (P = 0.0001). There were no statistically significant differences in serum ln COMP levels between African American men and women. CONCLUSION: Serum COMP levels vary by ethnicity and sex. These factors should be considered in the derivation of standards using this, and possibly other, potential biomarkers of OA.

Black or African American↗
PubMed2004

Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years.

OBJECTIVE: In many patients with knee osteoarthritis (OA), the disease progresses, and there is loss of cartilage; in others, the disease stabilizes with time. Previous studies have demonstrated that concentrations of serum proteins that reflect joint tissue metabolism can identify knees that will deteriorate, leading to the suggestion that OA disease activity is phasic or cyclical. The aim of the current study was to determine whether longitudinal measurements of one such protein, serum cartilage oligomeric matrix protein (COMP), are related to disease outcome over a 5-year period. METHODS: Serum COMP levels were measured by enzyme-linked immunosorbent assay at study entry and every 6 months thereafter in 115 patients with knee pain and OA of mainly the tibiofemoral joint. Cartilage loss was determined from knee radiographs taken at entry and at 24, 36, and 60 months. Disease progression was defined as either a reduction in the tibiofemoral joint space width by at least 2 mm or total knee replacement (TKR) in either knee at followup. COMP concentrations at baseline and the area under the curve (AUC) of measurements obtained over 5 years were compared between progressors and nonprogressors by Student's 2-tailed t-test. The patterns and probability of progression according to TKR or > or =2 mm of narrowing of the tibiofemoral joint space were analyzed by logistic regression models. RESULTS: The mean +/- SD ages of the progressors and nonprogressors were 64.2 +/- 7.8 years and 63.3 +/- 10.6 years, respectively, and the proportion of females was 51% and 56%, respectively. Of the 37 patients whose OA progressed (22 by TKR and 15 by > or =2-mm reduction in tibiofemoral joint space), 13 lost cartilage during the first 2 years, and 18 lost cartilage during the last 2 years. The mean +/- SD serum COMP concentration at baseline was significantly higher in the progressors compared with the nonprogressors (14.12 +/- 3.39 units/liter versus 12.62 +/- 3.25 units/liter; P < 0.036). Serum COMP levels rose significantly after TKR; however, after allowing for the effect of TKR, the AUC/month was significantly higher in the progressors compared with the nonprogressors (12.52 +/- 2.71 versus 10.82 +/- 2.71; P < 0.003). Serum COMP concentrations were higher during periods of radiographic progression and identified periods of progression that were nonlinear. Logistic regression analysis showed that on average, a 1-unit increase in serum COMP levels increased the probability of radiographic progression by 15%. CONCLUSION: The data suggest that serum COMP is related to progressive joint damage in knee OA. The patterns of progression for the early and late progressors are consistent with the hypothesis that knee OA progression is episodic or phasic. Large between-subject variation precludes the use of individual values to predict progression with confidence. However, sequential measurements of serum COMP levels may identify patients whose OA is likely to progress over the next year or two.

Aged↗
PubMed2006

Association of higher levels of serum cartilage oligomeric matrix protein and N-telopeptide crosslinks with the development of radiographic hip osteoarthritis in elderly women.

OBJECTIVE: To examine the association of baseline concentrations of serum cartilage oligomeric matrix protein (COMP) and serum N-telopeptide crosslinks (NTX) with the development and progression of radiographic hip osteoarthritis (RHOA) in elderly women. METHODS: Pelvic radiographs were obtained a mean of 8.3 years apart from white women > or =65 years of age enrolled in the Study of Osteoporotic Fractures. Random sampling from a cohort of 5,928 subjects was performed, with subjects ( approximately 200 per group) assigned to nested case-control studies, one focusing on RHOA incidence and the other on RHOA progression. Baseline serum levels of COMP and NTX were measured by enzyme-linked immunosorbent assay in duplicate. Odds ratios (ORs) and 95% confidence intervals (95% CIs), indicating the likelihood of baseline serum COMP and NTX levels to be predictive of the development or progression of RHOA, were calculated using logistic regression analysis, with adjustment for potential covariates. RESULTS: At baseline, incident cases of RHOA were associated with higher serum levels of COMP and NTX (P < 0.05 for each) compared with the no RHOA control group. Higher baseline serum COMP and NTX levels were associated with an increased risk of incident RHOA compared with the no RHOA group, with an adjusted OR of 1.31 per SD increase in COMP (95% CI 1.02-1.68) and adjusted OR of 1.38 per SD increase in NTX (95% CI 1.07-1.79). In this community-based cohort, progression of RHOA was modest. However, there was a trend toward increased risk of RHOA progression with higher baseline COMP and NTX levels. CONCLUSION: These data suggest that serum levels of COMP and NTX are modest risk markers for the development of RHOA in a community-based cohort of elderly white women.

Aged↗
PubMed2006

The heritable determinants of cartilage oligomeric matrix protein.

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a cartilage matrix macromolecule. The protein is detectable in serum and has been investigated as a biomarker of osteoarthritis (OA). An association between COMP and OA has been shown, yet the precise factors governing serum levels of COMP remain unclear. The aim of this study was to determine whether genetic factors influence serum levels of COMP. METHODS: A classic twin study was conducted using COMP levels in serum obtained from healthy female twin volunteers. COMP levels were determined by an inhibition enzyme-linked immunosorbent assay method. The heritability of COMP was determined by comparing correlation among 160 monozygotic and 349 dizygotic twin pairs. Data on potential confounding factors, including age, body mass index, and the presence of OA as assessed by hand, hip, and knee radiographs, were included in the analysis. RESULTS: Serum levels of COMP showed a correlation of 0.72 (95% confidence interval [95% CI] 0.65-0.80) among monozygotic twin pairs and 0.47 (95% CI 0.39-0.55) in dizygotic pairs. This equated to an estimated heritability for COMP of 40% (95% CI 20-60%). Although age and body mass index were found to be significantly associated with COMP in regression analysis, taking the effects of these factors into account did not influence the estimate of heritability. CONCLUSION: This study showed that heritable factors influence serum levels of the cartilage matrix biomarker COMP. Together with other published data, the results suggest that genetic factors operate at an early stage in the etiologic pathways that influence the development of radiographically discernible OA.

Adult↗
PubMed2006

Expression of mutant cartilage oligomeric matrix protein in human chondrocytes induces the pseudoachondroplasia phenotype.

Over 70 mutations in the cartilage oligomeric matrix protein (COMP), a large extracellular pentameric glycoprotein synthesized by chondrocytes, have been identified as causing two skeletal dysplasias: multiple epiphyseal dysplasia (MED/EDM1), and a dwarfing condition, pseudoachondroplasia (PSACH). These mutations induce misfolding of intracellular COMP, resulting in retention of the protein in the rough endoplasmic reticulum (rER) of chondrocytes. This accumulation of COMP in the rER creates the phenotypic enlarged rER cisternae in the cells, which is believed to compromise chondrocyte function and eventually cause cell death. To study the molecular mechanisms involved with the disease, we sought to develop an in vitro model that recapitulates the PSACH phenotype. Normal human chondrocytes were transfected with wildtype (wt-) COMP or with mutant COMP (D469del; mt-) recombinant adenoviruses and grown in a nonattachment redifferentiating culture system that provides an environment allowing formation of a differentiated chondrocyte nodule. Visualization of normal cells expressing COMP suggested the hallmarks of the PSACH phenotype. Mutant COMP expressed in normal cells was retained in enlarged rER cisternae, which also retained IX collagen (COL9) and matrilin-3 (MATN3). Although these proteins were secreted normally into the ECM of the wt-COMP nodules, reduced secretion of these proteins was observed in nodules composed of cells transfected with mt-COMP. The findings complement those found in chondrocytes from PSACH patient growth plates. This new model system allows for production of PSACH chondrocyte pathology in normal costochondral chondrocytes and can be used for future mechanistic and potential gene therapy studies.

Achondroplasia↗
PubMed2000

Transient expression of megakaryocyte-derived protein immunoreactive with an antiserum to cartilage oligomeric matrix protein in developing rat liver.

We analyzed a megakaryocyte-derived protein immunoreactive with an antiserum to cartilage oligomeric matrix protein (COMP) in the developing rat liver. Staining with the anti-COMP antiserum in the developing rat liver increased during embryogenesis, and was strongest in the livers of 17-day-old embryos. However, staining in the liver was not detected at eight days after birth or thereafter. The stained cells were found to be megakaryocytes. We partially purified the protein showing cross-reaction with the antiserum to COMP from a megakaryocyte-rich cells fraction in 17-day-old embrionic rat livers. The molecular weight of this protein (approximately 95 kDa) was close to the molecular weight of COMP (105 kDa). Amplification of an RT-PCR fragment (225 bp) corresponding to part of COMP mRNA was detected in cartilage, but not in megakaryocytes of fetal liver or bone marrow. Based on these results, the fetal rat liver megakaryocyte-derived protein that reacted with the antiserum against COMP was thought to contain a common epitope with COMP from cartilage, but to be a different protein from COMP.

Acetylcholinesterase↗
PubMed1994

Characterization of human and mouse cartilage oligomeric matrix protein.

Cartilage oligomeric matrix protein (COMP) is a 524,000-Da protein that is expressed at high levels in the territorial matrix of chondrocytes. The sequences of rat and bovine COMP indicate that it is a member of the thrombospondin gene family. In this study, we have cloned and sequenced human COMP. Phylogenetic analysis using progressive sequence alignment and two parsimony-based algorithms indicates that the COMP gene and a precursor of the thrombospondin-3 and -4 genes were produced by a gene duplication that occurred 750 million years ago. An interspecific backcross mapping panel has been used to map the murine COMP gene to the central region of mouse chromosome 8. Southern blot analysis of a somatic cell hybrid DNA panel and in situ hybridization to human metaphase chromosomes indicate that the human COMP gene is located on chromosome 19 in band p13.1. These data confirm and extend the known regions of homology between human and mouse chromosomes and establish that COMP, like thrombospondin-1, -2, -3, and -4, is present in the human and mouse genomes.

Animals↗
PubMed2002

Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects.

We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects.

Adolescent↗
PubMed2005

Cartilage oligomeric matrix protein in serum in systemic lupus erythematosus and knee osteoarthritis. Preliminary communication.

The cartilage oligomeric matrix protein (COMP) is a glycoprotein, which occurs mainly in an articular cartilage. The amount of this protein increases under the influence of cytokines and growth factors. As a result of various diseases that cause damage to cartilage, fragments of matrix protein are released into synovial fluid and then into blood. The assessment of matrix protein level in serum, for example COMP, permits the establishment of the degree of cartilage damage in inflammatory joint diseases, and permits observation of the effectiveness of the treatment. Blood was collected from 30 systemic lupus erythematosus (SLE) patients, and from 30 patients with knee osteoarthritis (OA) who constituted the control group. Serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value of the serum COMP level in SLE patients was 11.3+/-3.7 U/l. According to correlation coefficients, serum COMP level is independent of patients' age, disease duration and the clinical picture of SLE. No correlation was found between serum COMP level and bone mass density (BMD) changes. In SLE patients with decreased haemoglobin levels (<11.0 g/dl) values compared with patients with normal haemoglobin level, the serum COMP level was observed to be significantly higher (P<0.05). Both in SLE patients with erythrocyte sedimentation rate (ESR) values over 60 mm/h and in patients with ESR values below 60 mm/h, the serum COMP level was observed to be significantly higher (P<0.05). A significant positive correlation was found between serum COMP level and ESR value, as well as a number of thrombocytes. Negative correlation occurred between the serum COMP level and the value of haemoglobin. The average value of COMP in OA patients was 10.4+/-2.7 U/l. No correlation was found between serum COMP level and patients' age and disease duration. There was correlation between the serum COMP level and the T-score value of densitometry examinations in OA patients. No statistical differences were found between the average serum COMP levels for SLE and OA patients.

Adult↗
PubMed2006

Serum levels of cartilage oligomeric matrix protein (COMP): a rapid decrease in patients with active rheumatoid arthritis undergoing intravenous steroid treatment.

To examine the influence of intravenous steroid-treatment (IST) on serum levels of Cartilage oligomeric matrix protein (COMP) in patients with active rheumatoid arthritis (RA). Serum levels of COMP and C-reactive protein (CRP) were measured in 12 patients with highly active RA (Steinbrocker stages II-IV) and in 5 patients with highly active reactive arthritis (ReA) (positive testing for HLA-B27) before starting daily IST. Patients received a total steroid dosage between 100 and 500 mg of prednisolone. COMP was measured by a commercially available sandwich-type ELISA-kit developed by AnaMar Medical AB, Sweden. Statistical evaluation was calculated by paired t test. In the RA group, COMP levels ranged from 6.3 to 19.4 U/l (mean 12.9 U/l), CRP from 5 to 195 mg/l (mean 77.8 mg/l), the COMP levels of the ReA group ranged from 5.1 to 7.4 U/l (mean 7.9 U/l), the CRP levels from 13 to 126 mg/l (mean 49 mg/l). We found a significant difference between the initial COMP levels in RA+ and ReA patients (P<0.005). In contrast to the ReA group, serum-COMP levels of RA+ patients (P<0.004) and the VAS (P<0.0001) decreased significantly within 2-10 days after the first treatment with steroids. The CRP levels remained unchanged in both groups. Our results indicate that the intravenous treatment with steroids in patients with highly active RA leads to a significant decrease of cartilage degradation. COMP seems to be a valuable parameter not even as a prognostic factor, but as a marker for monitoring the therapy response in patients with RA.

Adult↗
PubMed1998

Persistent high serum levels of cartilage oligomeric matrix protein in a subgroup of patients with traumatic knee injury.

The objective was to assess whether changes of cartilage oligomeric matrix protein (COMP) serum levels can predict the development of osteoarthritis following traumatic knee injury. Sera and synovial fluids were acquired at surgery (T0) and postoperatively during the first (T1) and second (T2) year from 30 knee-injured patients. COMP levels and anti-COMP autoantibodies were quantified by ELISA. Radiographs and patient questionnaires were used to assess outcomes. At T0, compared with controls (1.6 +/- 1.6 micrograms/ml), the serum COMP concentration was significantly elevated (6.5 +/- 2.8 micrograms/ml) with a tendency to further increase (T0 vs. T1, P = 0.076) and subsequently decrease (T1 vs. T2, P = 0.074). However, individual variations are observed, e.g. persistently high (8/30) or increasing (T0 to T2, 8/30) serum COMP. Ten of these patients have elevated COMP at T2 that increased from T0. COMP levels in serum and synovial fluid correlated significantly (P = 0.012). Interestingly, some patients who revealed increasing serum levels of COMP from T0 to T2 displayed anti-COMP autoantibodies. These data suggest that local immune response could contribute to further joint damage. The subgroup of 10 patients (33%) with elevated and increasing serum COMP levels and in particular the patients with antibodies against cartilage matrix molecules appear at increased risk for developing posttraumatic osteoarthritis.

Adult↗
PubMed2002

[Functional capacity and cartilage oligomeric protein (COMP) in serum of patients with maturity-onset polyarthritis].

OBJECTIVE: To compare late onset with adult onset rheumatoid arthritis. METHODS: Fifty-eight patients with late onset rheumatoid arthritis (LORA) were compared to 117 patients with adult onset rheumatoid arthritis (AORA) with respect to clinical and functional parameters. Furthermore, in 104 patients serum cartilage oligomeric matrix protein (COMP) was measured. Results were compared by means of ANOVA and possible influences of age, gender and clinical parameters were evaluated by Spearman rank correlation. RESULTS: Except a different distribution in gender (40% males in the LORA group) and a higher ESR, no differences could be found with respect to clinical parameters. However, a significantly higher HAQ score and significantly higher serum-COMP levels could be shown in the LORA group. HAQ scores correlated not only with disease activity parameters (C-reactive protein, disease activity score) but also with the age. Serum-COMP levels did show a correlation with the age as well, but not with disease activity. CONCLUSION: It is concluded that the higher serum-COMP levels in late onset rheumatoid arthritis could be due to concomitant osteoarthritic processes in larger joints, which are not symptomatic. The age dependence of the HAQ score is only weak, but may be the reason why patients with LORA show a worse functional capacity compared to patients with adult onset rheumatoid arthritis.

Activities of Daily Living↗
PubMed1999

[Cartilage oligomeric matrix protein (COMP): the role of a non-collagen cartilage matrix protein as a marker of disease activity and joint destruction in patients with rheumatoid arthritis and osteoarthritis].

UNLABELLED: Today, we can assess criteria to predict the tissue destruction and progression of Rheumatoid Arthritis (RA) and Osteoarthritis (OA) only in a late stage of the disease. It would be an advantage to have biochemical markers of disease activity and joint destruction to optimize therapy. PATIENTS AND METHODS: In this cross-sectional study with 37 RA and 20 OA patients (disease duration 119 +/- 130 months for RA and 41 +/- 73 months for OA), ESR, CRP, disease activity score (DAS), the functional status of RA (American College of Rheumatology), and the radiological scoring systems of Larsen and Kellgren/Lawrence, respectively, were used as parameters for disease activity and joint destruction. Cartilage oligomeric matrix protein (COMP) was measured with an enzyme-linked immunosorbent assay (ELISA) in serum and synovial fluid, COMP fragments with immunoblot in the synovial fluid. RESULTS: The mean COMP value in synovial fluid was 38 ug/ml (RA) and 46 ug/ml (OA); 6.5 ug/ml (RA) and 3.4 ug/ml (OA) in serum. RA patients had a higher amount of small COMP fragments in synovial fluid than OA patients. In RA patients, there was a significant positive correlation between disease activity (DAS) and COMP in synovial fluid and serum, a negative correlation between functional status of RA and serum COMP and between radiologic joint destruction of the knee and serum COMP. In OA patients, there was a significant correlation of joint space width and synovial fluid COMP. DISCUSSION: A high clinical disease activity (DAS) correlated with high COMP values in serum and synovial fluid and with increasing proteolytic activity (higher amount of small COMP fragments especially in RA). An increased turnover of cartilage matrix in joint inflammation might explain this correlation. The correlation of decreased COMP with decreased functional status in RA and increased joint destruction is compatible with a loss of cartilage and less turnover. The correlation between joint space width and increased COMP in OA patients with short disease duration might be explained with a higher turnover of the cartilage matrix in the early stage of the disease.

Adult↗
PubMed1998

Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are common skeletal dysplasias with impaired enchondral ossification and premature degenerative joint disease. The two disorders were in the past considered to be distinct clinical entities; however, recent studies have proven that both diseases can result from mutations of the gene encoding cartilage oligomeric matrix protein (COMP). To characterize further COMP mutations and investigate phenotype-genotype relationships, we screened this gene in 15 patients with PSACH or MED by directly sequencing polymerase chain reaction products from genomic DNA. We identified ten mutations involving conserved residues among the eight calmodulin-like repeats of the gene product: seven were novel missense mutations in exons 9, 10, 11, 13 or 14, and the other three resulted from deletion of one of the five GAC repeats in exon 13. We have found that the GAC repeats in the 7th calmodulin-like repeat in exon 13 represent a hot-spot for mutation, and that mutations in the 7th calmodulin-like repeat produce severe PSACH phenotypes while mutations elsewhere in the gene exhibit mild PSACH or MED phenotypes. These genotype-phenotype correlations may facilitate molecular diagnosis and classification of PSACH and MED, and provide insight into the relationship between structure and function of the COMP gene product.

Achondroplasia↗
PubMed2003

Identification of cartilage oligomeric matrix protein (COMP) gene mutations in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.

Mutations in the cartilage oligomeric matrix protein (COMP) gene are responsible for two dominantly inherited skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). Mutation analysis of the COMP gene in Korean patients with PSACH and MED was performed. All nine patients with PSACH had mutations in the COMP gene, while three of the five patients with MED had detectable COMP mutations. Eight mutations, including three novel mutations, were identified in the COMP gene in the patients with PSACH and MED. Six mutations were found within the calmodulin-like repeats (CLRs) domain, especially in the seventh CLR and the other two mutations were in exon 16 outside of CLRs, which encode the C-terminal globular domain. Among the three novel mutations, two were missense mutations (Asp473Tyr, Asp482His) and one was a consecutive two-codon deletion, delAspAsp(469-473) in the five consecutive aspartic acid residues. All three novel mutations produced the PSACH phenotype.

Adolescent↗
PubMed2001

Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.

Osteoarthrosis (OA) is a common cause of musculoskeletal disability characterized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to be determined. Hereditary osteochondral dysplasias produce severe, early-onset OA and hence are models for common idiopathic OA. Among them are pseudoachondroplasia and multiple epiphyseal dysplasia, both of which are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefore, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gene with their flanking intron sequences and the promoter region. We identified 16 polymorphisms, of which 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was no significant difference in haplotypes. These results do not support an association between COMP and OA in the Japanese population.

Cartilage↗
PubMed1994

The thrombospondin-like chains of cartilage oligomeric matrix protein are assembled by a five-stranded alpha-helical bundle between residues 20 and 83.

The N-terminal fragment of rat cartilage oligomeric matrix protein (COMP), comprising residues 20-83, was over-expressed in E. coli and purified under non-denaturing conditions. The fragment forms pentamers similar to the assembly domain of the native protein. Its five chains can be covalently linked in vitro by oxidation of cysteines 68 and 71. The fragment adopts a predominantly alpha-helical structure as judged by circular dichroism spectroscopy. On the basis of these findings we propose the model of a five-stranded alpha-helical bundle for the assembly domain of COMP. The studied sequence is conserved in thrombospondins 3 and 4 thus raising the possibility that these proteins are also pentamers.

Amino Acid Sequence↗