Cartilage oligomeric matrix protein (COMP) is a potential biomarker for joint destruction associated with osteoarthritis, which is first and best investigated biomarkers to reflect osteoarthritis occurs, progress and the prognosis. In this article, multiple uses and related reports of COMP are summarized briefly to promote further investigation of COMP.
Biomarkers ; blood ; Cartilage Oligomeric Matrix Protein ; Extracellular Matrix Proteins ; blood ; chemistry ; metabolism ; Glycoproteins ; blood ; chemistry ; metabolism ; Humans ; Matrilin Proteins ; Osteoarthritis ; blood ; diagnosis ; Prognosis

OBJECTIVETo perform mutation analysis for a female with multiple epiphyseal dysplasia (MED) and provide pre-symptomatic and prenatal diagnosis.

METHODSMutation screening of cartilage oligomeric matrix protein (COMP) gene was carried out through targeted next-generation DNA sequencing and Sanger sequencing.

RESULTSA novel c.956 A>T resulting in substitution of Aspartic acid 319 for Valine (p.Asp319Val) has been identified in exon 9 of the COMP gene in the patient. As predicted by a SIFT software, above mutation can cause damage to the structure of COMP protein.

CONCLUSIONA novel c.956 A>T substitution mutation has been identified in a patient featuring MED.

Adult ; Base Sequence ; Cartilage Oligomeric Matrix Protein ; Exons ; Extracellular Matrix Proteins ; genetics ; Female ; Glycoproteins ; genetics ; Humans ; Matrilin Proteins ; Mutation ; Osteochondrodysplasias ; diagnosis ; genetics ; Polymorphism, Single Nucleotide ; Sequence Alignment

Identification of genetic risk factors is the hotspot of adolescent idiopathic scoliosis (AIS). Through candidate gene approach and genome-wide association studies (GWAS), some genes were preliminary identified. To review AIS related genes,and construct the gene network map of AIS gene. We searched on NCBI PubMed and Web of Science database using search terms "adolescent idiopathic scoliosis" and "gene", to classify induction genes. We then constructed gene diagram using string-db. We found 35 AIS genes relating to connective tissue, nervous system active substances, melatonin synthesis and metabolism, puberty and growth, and genes whose function is unknown. Gene diagram shows that a network relationship between gene and other genes,in which IL6, ESR1, ESR2, VDR, TGFB1, IGF1 gene may as the key gene about AIS' genetic mechanism. Two sites of 3 GWAS results outside the network, it is suggesting new pathway that need to be explored. The study about AIS susceptibility gene is still preliminary, requiring in-depth research to identify the new networks.
Adolescent ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Insulin-Like Growth Factor I ; genetics ; Matrilin Proteins ; genetics ; Scoliosis ; genetics ; Transforming Growth Factor beta1 ; genetics

OBJECTIVESTo study cartilage oligomeric matrix protein (COMP) mRNA and protein expression in normal pancreas, chronic pancreatitis (CP), and pancreatic cancer tissues.

METHODSTissues from 15 cases of normal pancreas, 14 cases of chronic pancreatitis and 14 cases of pancreatic cancer were analyzed by Northern blot, Western blot, in situ hybridization and immunohistochemistry.

RESULTSCOMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues.

CONCLUSIONCOMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this molecular in acinar cell dysfunction in CP.

Blotting, Northern ; Blotting, Western ; Cartilage Oligomeric Matrix Protein ; Dimerization ; Extracellular Matrix Proteins ; chemistry ; genetics ; metabolism ; Glycoproteins ; chemistry ; genetics ; metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Matrilin Proteins ; Pancreas ; metabolism ; pathology ; Pancreatic Neoplasms ; metabolism ; pathology ; Pancreatitis, Chronic ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism

OBJECTIVETo select sub-clinical patients with symptoms of knee osteoarthritis (KOA) without X-ray changes by measuring the serum level of cartilage oligomeric matrix protein (COMP) with ELISA, so as to diagnose and treat patients with knee osteoarthritis at early stage.

METHODSThe 115 patients with KOA or with symptomatic primary KOA were enrolled from August 2007 to September 2009, which was OA group; and 35 healthy people in the control group. In OA group, there were 55 males and 60 females,ranging in age from 39 to 76 years, with an average of (55 +/- 13.32) years; the body mass index (BMI) ranged from 15.1 to 29.8; the disease course ranged from 6 to 60 months. In the control group, there were 16 males and 19 females, ranging in age from 36 to 77 years, with an average of (53 +/- 12.53) years; the BMI ranged from 14.8 to 29.2. Patients with symptomatic primary knee OA of Kellgren-Lawrence (K-L) grade I-IV were evaluated. Serum level of COMP and its correlation with OA grade were analyzed by ELISA method. The patients were treated with Celecoxib capsules. The patients in OA group were followed up, and the duration ranged from 24 to 38 months (averaged, 33.4 months), and the serum level of COMP were analyzed before and after treatment.

RESULTSThe serum level of COMP in the control group varied with age (t= 2.50, P=0.02). The serum level of COMP did not correlate with gender (control group: t=0.98, P=0.34; OA group: t=0.18, P= 0.86), BMI (control group: t=0.56, P=0.92; OA group: t=0.17, P=0.85) and smoking (control group: t=1.89, P=0.08; OA group: t=0.70, P=0.49). The serum level of COMP was higher in the patients with higher K-L grades than in the patients with lower K-L grades (F=15.56, P=0.001) . The sub-clinical KOA patients without X-ray changes can be detected significant higher COMP levels than sub-clinical patients with other diseases (t=2.55, P=0.03). Therefore, according to this method, subclinical OA patients can be detected from people with other sub-clinical diseases successfully.

CONCLUSIONThe serum level of COMP can be used as a potential prognostic marker to diagnose KOA.

Adult ; Aged ; Biomarkers ; blood ; Body Mass Index ; Cartilage Oligomeric Matrix Protein ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins ; blood ; Female ; Glycoproteins ; blood ; Humans ; Male ; Matrilin Proteins ; Middle Aged ; Osteoarthritis, Knee ; blood ; diagnosis

OBJECTIVETo explore the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis (KOA).

METHODSFrom November 2009 to January 2011,70 patients with KOA combined with knee effusion among outpatient and inpatient were analyzed retrospectively. Among the patients, 12 patients were male, 58 patients were female,ranging in age from 46 to 75 years,with a mean age of (59.66 +/- 9.93) years. The clinical symptoms were evaluated by WOMAC, the imaging of KOA was assessed by K-L score and WORMS, and COMP and CTX- II were measured respectively by ELISA. The correlation analyses and multiple linear regression analysis were studied to determine associations among biomarkers, clinical variables and radiographic findings of knee joints.

RESULTSThe average scores of WOMAC and WORMS were (57.50 +/- 8.20) and (64.54 +/- 16.45) respectively. The median of CTX- II nd COMP were 2.42 ng/ml and 4.56 ng/ml respectively. Grouped by less than the lowest quartile and more than the highest quartile of WORMS, COMP was significantly different (Z=2.04, P=0.039), but there was no significant difference in CTX-II (Z=0.79, P=0.427). WORMS were positively correlated with WOMAC and K-L score (r=0.777, P<0.01; r=0.716, P<0.01; respectively); WOMAC was also positively correlated with K-L score (r=0.692, P<0.01). WORMS's cartilage, osteophytes and synovitis were positively correlated with WOMAC, K-L score and COMP respectively (r=0.771, P<0.01; r=0.509, P<0.01; r=0.917, P<0.01). It was determined by stepwise regression that the KOA was mainly affected by WORMS, K-L score (P=0.015, P=0.025 respectively) when WOMAC as a dependent variable, age, gender, K-L score, WORMS, COMP and CTX- II as independent variables (F=20.327, P<0.01).

CONCLUSIONWORMS has a better reference value for diagnosis of KOA. The expression of COMP is high in the synovial fluid when WORMS at the high point. The clinical symptoms of knee osteoarthritis are mainly affected by WORMS and K-L score.

Aged ; Cartilage Oligomeric Matrix Protein ; Collagen Type I ; analysis ; Extracellular Matrix Proteins ; analysis ; Female ; Glycoproteins ; analysis ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Matrilin Proteins ; Middle Aged ; Osteoarthritis, Knee ; diagnosis ; metabolism ; physiopathology ; Peptides ; analysis

BACKGROUNDPseudoachondroplasia (PSACH) is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein (COMP). Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation. There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH. Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH.

METHODSA family with three patients and a sporadic case were recruited. Genomic and phenotypic data were recorded. The diagnosis of PSACH was made on the base of clinical evaluation. The genomic DNA was extracted from peripheral blood leukocytes. The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein.

RESULTSA deletion (c.1447-1455del) was identified in exon 13 in the sporadic case. The mean serum COMP concentrations of four patients (3.12+/-2.28) were significantly lower than those of control group (10.86+/-2.21, P<0.05). There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls.

CONCLUSIONSMutations in COMP gene are responsible for the PSACH. Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.

Cartilage Oligomeric Matrix Protein ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Exons ; genetics ; Extracellular Matrix Proteins ; blood ; genetics ; Female ; Glycoproteins ; blood ; genetics ; Humans ; Male ; Matrilin Proteins ; Mutation ; Osteochondrodysplasias ; blood ; genetics ; Pedigree ; Polymerase Chain Reaction

OBJECTIVESTo investigate the association between matrilin-1 gene polymorphism and bracing effectiveness in adolescent idiopathic scoliosis girls.

METHODSIn a prospective study, AIS girls treated with standard bracing from January 2005 to December 2008 were included and followed up. All subjects of the study met the following criteria: female; skeletally immature (Risser sign grade 0 - 3); before menarche or < 1.5 years after menarche; Cobb angle 20 degrees - 40 degrees ; scoliosis caused by congenital, neuromuscular and other cause were excluded; no evidence of bone diseases, metabolic diseases or other condition known to affect bone metabolism; no history of bracing before onset; follow-up with an interval of 3 months, and total follow-up time > 2 years. Subjects met one of the following conditions was excluded: the final follow-up time < 2 years; bad compliance (ratio of the actual daily wearing time to proposed wearing time) of bracing (< 75%); change of bracing without doctor's order. Cobb angle of major curve was recorded before the bracing initiation and at the final follow-up. A progression of 6 degrees or more was considered to be a failure of bracing. The rs1149048 polymorphism in promoter of matrilin-1 gene was chosen for genotyping by PCR-RFLP method. Differences in age at initial visit, Risser sign, Cobb angle and genotype distribution were compared between brace failure and brace success groups.

RESULTSSeventy seven patients with AIS were included, with a mean age at (13.0 +/- 1.5) years and a mean Cobb angle at (30.3 +/- 11.9) degrees . After an average duration of 2.6 years follow-up, mean Cobb angle was 30.3 degrees +/- 11.9 degrees . There were 19 cases (24.7%) in bracing failure and 58 cases (75.3%) in bracing success. The initial Cobb angle was larger in bracing failure group compared with bracing success group (P > 0.05). Patients with double major curve were found to have the lowest bracing failure rate (19.4%), but there was no significant difference compared with other curve patterns. Bracing failure rate was marked higher in individual with genotype GG (66.7%) than that with genotype AA or AG.

CONCLUSIONSProgression of most mild or moderate AIS can be managed by early standardized bracing treatment. It is shown that large initial Cobb angle and genotype GG of matrilin-1 gene are indicative of less bracing effectiveness.

Adolescent ; Braces ; Cartilage Oligomeric Matrix Protein ; Child ; Extracellular Matrix Proteins ; genetics ; Female ; Follow-Up Studies ; Genotype ; Glycoproteins ; genetics ; Humans ; Matrilin Proteins ; Polymorphism, Genetic ; Prospective Studies ; Scoliosis ; genetics ; therapy ; Treatment Outcome

OBJECTIVETo determine the circulating matrilin-1 levels in adolescent idiopathic scoliosis (AIS), and to investigate its potential role in etiopathogenisis of AIS.

METHODSThis study population consisted of 25 patients with AIS from June 2006 to March 2007 and 25 age-matched normal controls. All subjects of the study met the following criteria: no evidence of bone diseases, metabolic diseases or growth disturbances; no evidence of systemic illness or other condition known to affect bone metabolism; and no history of recent steroid intake and surgery of congenital cardiopathy. The maximum Cobb angle and curve pattern of AIS group were recorded. All AIS patients were categorized by progressive and non-progressive groups. Progression to a severe curve was defined per usual clinical criteria (progression to a > 40 degrees curve in an individual still growing or progression to a > 50 degrees curve in an adult). Measurements of genotype by PCR-RFLP methods and circulating matrilin-1 by ELISA assay were performed in both AIS and control groups. The circulating matrilin-1 levels were compared between AIS and control groups, and also among different genotype individuals. The relationship between matrilin-1 levels and cure progression were also analyzed.

RESULTSCompared with control group, a marked decrease of plasma matrilin-1 levels was found in AIS groups (P = 0.0002). Matrilin-1 levels of both AIS and control groups with GG genotype tended to be lower than with AA and AG genotypes, and this trend was stronger in AIS groups. Compared with non-progressive AIS group, plasma matrilin-1 levels in progressive AIS group were significantly lower.

CONCLUSIONSThere is an association between matrilin-1 levels and curve progression. Measurement of circulating matrilin-1 levels is helpful for early screening and diagnosis of AIS, and it may be considered as an independent index to predict curve progression.

Adolescent ; Adult ; Cartilage Oligomeric Matrix Protein ; Child ; Extracellular Matrix Proteins ; blood ; genetics ; Female ; Follow-Up Studies ; Genotype ; Glycoproteins ; blood ; genetics ; Humans ; Male ; Matrilin Proteins ; Scoliosis ; blood ; diagnosis ; Young Adult

OBJECTIVETo investigate the association of matrilin-1 gene polymorphisms with adolescent idiopathic scoliosis (AIS) risk.

METHODSThis study population consisted of 419 patients with AIS and 460 healthy controls. The maximum Cobb angle of AIS patients was recorded. For initial screening, the 7 tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant associations in additional sample of 222 cases and 288 controls. Single-marker and haplotype analysis were employed. Genotyping was performed by PCR-RFLP method.

RESULTSWe found that allele G of rs1149048 was a significant predisposition allele of AIS (P = 0.0027, OR = 1.34 within 95% CI = 1.11 approximately 1.62), and individuals with genotype GG had a higher risk for AIS compared to AA + AG (P = 0.0008, OR = 1.61 within 95% CI = 1.22 approximately 2.12). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. And a significantly higher in maximum Cobb angle was found in patients with GG genotype (P = 0.002).

CONCLUSIONSIt is concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region is associated with both susceptibility and disease severity in AIS.

Adolescent ; Cartilage Oligomeric Matrix Protein ; Case-Control Studies ; Child ; Extracellular Matrix Proteins ; genetics ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genotype ; Glycoproteins ; genetics ; Humans ; Linkage Disequilibrium ; Male ; Matrilin Proteins ; Polymorphism, Single Nucleotide ; Scoliosis ; genetics ; Young Adult