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1.
Journal of Peking University(Health Sciences) ; (6): 34-39, 2020.
Article in Chinese | WPRIM | ID: wpr-942138

ABSTRACT

OBJECTIVE@#To detect the expression of cartilage oligomeric matrix protein (COMP) in the synovial chondromatosis of the temporomandibular joint (TMJSC), and to discuss the possible interactions between COMP, transforming growth factor (TGF)-β3, TGF-β1 and bone morphogenetic protein-2 (BMP-2) in the development of this neoplastic disease.@*METHODS@#Patients in Peking University School and Hospital of Stomatology from January 2011 to February 2020 were selected, who had complete medical records, TMJSC was verified histologically after operation. The expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in the TMJSC of the temporomandibular joint were detected by immunohistochemistry and quantitative real-time PCR (RT-PCR) at the protein level and mRNA level respectively, compared with the normal synovial tissue of temporomandibular joint. The histological morphology, protein expression and distribution of TMJSC tissues were observed microscopically, and the positive staining proteins were counted and scored. SPSS 22.0 statistical software was used to analyze the expression differences between the related proteins in TMJSC tissue and the normal synovial tissue of temporomandibular joint and to compare their differences. P < 0.05 indicated that the difference was statistically significant.@*RESULTS@#Immunohistochemical results showed that the positive expression of COMP in TMJSC tissues was mostly found in synovial tissues and chondrocytes adjacent to synovial tissues, and the difference was statistically significant, compared with the normal temporomandibular joint synovial tissues. The positive expression of COMP was significantly different between recurrent TMJSC and non-recurrent ones. The positive expressions of TGF-β3, TGF-β1 and BMP-2 were higher than the normal synovial tissue, and were also mostly found in the synovial cells and adjacent chondrocytes, which was further confirmed by Western blot. According to the RT-PCR results, the expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in TMJSC were higher than those in the normal synovial tissue.@*CONCLUSION@#The expression of COMP in TMJSC of temporomandibular joint increased significantly, compared with the normal synovial tissue. There may be interactions between COMP and cytokines related to the proliferation and differentiation, like TGF-β3, TGF-β1 and BMP-2, which may play a potential role in the pathogenesis of TMJSC.


Subject(s)
Humans , Cartilage Oligomeric Matrix Protein/genetics , Chondromatosis, Synovial , Synovial Membrane , Temporomandibular Joint , Transforming Growth Factor beta3
2.
Yonsei Medical Journal ; : 1081-1092, 2019.
Article in English | WPRIM | ID: wpr-762050

ABSTRACT

PURPOSE: Accumulating evidence suggests that microRNA-145 (miR-145) plays an important role in osteoarthritis (OA), which is a chronic progressive joint disease. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes metastasis in cancers and functions as a sponge for miR-145. However, the role of MALAT1/miR-145 in OA pathogenesis has not yet been elucidated. MATERIALS AND METHODS: The expression of MALAT1 and miR-145 was examined by quantitative real-time PCR; the interaction between miR-145, MALAT1 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 was verified by luciferase reporter assay. Correlations among MALAT1, miR-145, and ADAMTS5 were analyzed by Spearman rank analysis. Chondrocytes viability and cartilage extracellular matrix (ECM) degradation were investigated with cell viability assay and Western blotting analyzing expression of ADAMTS5, collagen type 2 alpha 1 (COL2A1), aggrecan (ACAN), and cartilage oligomeric matrix protein (COMP). RESULTS: MALAT1 was upregulated, and miR-145 was downregulated in OA samples and IL-1β-induced chondrocytes. Mechanically, miR-145 could directly bind to MALAT1 and ADAMTS5. Moreover, miR-145 expression was negatively correlated with MALAT1 and ADAMTS5 expression in OA patients, whereas MALAT1 and ADAMTS5 expression was positively correlated. Functionally, overexpression of MALAT1 inhibited chondrocyte viability and promoted cartilage ECM degradation in IL-1β-induced chondrocytes. In support thereof, MALAT1 silencing and miR-145 upregulation exerted the opposite effect in IL-1β-induced chondrocytes. Moreover, the effect of MALAT1 was counteracted by miR-145 upregulation, and ADAMTS5 restoration could abate miR-145 effects. CONCLUSION: An MALAT1/miR-145 axis contributes to ECM degradation in IL-1β-induced chondrocytes through targeting ADAMTS5, suggesting that MALAT1/miR-145/ADAMTS5 signaling may underlie human OA pathogenesis.


Subject(s)
Humans , Adenocarcinoma , Aggrecans , Blotting, Western , Cartilage Oligomeric Matrix Protein , Cartilage , Cell Survival , Chondrocytes , Collagen , Extracellular Matrix , Joint Diseases , Luciferases , Lung , Neoplasm Metastasis , Osteoarthritis , Porifera , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding , Temefos , Thrombospondins , Up-Regulation
3.
Tissue Engineering and Regenerative Medicine ; (6): 93-101, 2017.
Article in English | WPRIM | ID: wpr-649896

ABSTRACT

In this paper we report the differentiating properties of platelet-rich plasma releasates (PRPr) on human chondrocytes within elastomeric polycaprolactone triol–citrate (PCLT–CA) porous scaffold. Human-derived chondrocyte cellular content of glycosaminoglycans (GAGs) and total collagen were determined after seeding into PCLT–CA scaffold enriched with PRPr cells. Immunostaining and real time PCR was applied to evaluate the expression levels of chondrogenic and extracellular gene markers. Seeding of chondrocytes into PCLT–CA scaffold enriched with PRPr showed significant increase in total collagen and GAGs production compared with chondrocytes grown within control scaffold without PRPr cells. The mRNA levels of collagen II and SOX9 increased significantly while the upregulation in Cartilage Oligomeric Matrix Protein (COMP) expression was statistically insignificant. We also report the reduction of the expression levels of collagen I and III in chondrocytes as a consequence of proximity to PRPr cells within the scaffold. Interestingly, the pre-loading of PRPr caused an increase of expression levels of following extracellular matrix (ECM) proteins: fibronectin, laminin and integrin β over the period of 3 days. Overall, our results introduce the PCLT–CA elastomeric scaffold as a new system for cartilage tissue engineering. The method of PRPr cells loading prior to chondrocyte culture could be considered as a potential environment for cartilage tissue engineering as the differentiation and ECM formation is enhanced significantly.


Subject(s)
Humans , Blood Platelets , Cartilage Oligomeric Matrix Protein , Cartilage , Chondrocytes , Collagen , Elastomers , Extracellular Matrix , Fibronectins , Glycosaminoglycans , Laminin , Methods , Phenotype , Platelet-Rich Plasma , Real-Time Polymerase Chain Reaction , RNA, Messenger , Tissue Engineering , Up-Regulation
4.
Tissue Engineering and Regenerative Medicine ; (6): 732-739, 2016.
Article in English | WPRIM | ID: wpr-647609

ABSTRACT

Osteoarthritis (OA) of the knee is a degenerative joint disease caused by the progressive reduction of the articular cartilage surface that leads to reduced joint function. Cartilage degeneration occurs through gradual loss in extracellular matrix components including type II collagen and proteoglycan. Due to limited inherent self repair capacity of the cartilage, the use of cell-based therapies for articular cartilage regeneration is considered promising. Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells and are highly capable of multilineage differentiation which render them valuable for regenerative medicine. In this study, BM-MSCs were isolated from OA patients and were characterized for MSC specific CD surface marker antigens using flowcytometry and their differentiation potential into adipocytes, osteocytes and chondrocytes were evaluated using histological and gene expression studies. BM-MSCs isolated from OA patients showed short spindle shaped morphology in culture and expressed positive MSC related CD markers. They also demonstrated positive staining with oil red O, alizarin red and alcian blue following differentiation into adipocytes, osteocytes and chondrocytes, respectively. In addition, chodrogenic related genes such as collagen type II alpha1, cartilage oligomeric matrix protein, fibromodulin, and SOX9 as well as osteocytic related genes such as alkaline phosphatase, core-binding factor alpha 1, osteopontin and RUNX2 runt-related transcription factor 2 were upregulated following chondrogenic and osteogenic differentiation respectively. We have successfully isolated and characterized BM-MSCs from OA patients. Although BM-MSCs has been widely studied and their potential in regenerative medicine is reported, the present study is the first report in our series of experiments on the BMSCs isolated from OA patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.


Subject(s)
Humans , Adipocytes , Adipogenesis , Alcian Blue , Alkaline Phosphatase , Antigens, Differentiation , Bone Marrow , Cartilage , Cartilage Oligomeric Matrix Protein , Cartilage, Articular , Chondrocytes , Chondrogenesis , Collagen Type II , Core Binding Factors , Extracellular Matrix , Gene Expression , Joint Diseases , Joints , Knee , Mesenchymal Stem Cells , Osteoarthritis , Osteocytes , Osteogenesis , Osteopontin , Proteoglycans , Regeneration , Regenerative Medicine , Saudi Arabia , Transcription Factors
5.
Experimental Neurobiology ; : 55-70, 2015.
Article in English | WPRIM | ID: wpr-190710

ABSTRACT

Successful recovery from brain ischemia is limited due to poor vascularization surrounding the ischemic zone. Cell therapy with strong angiogenic factors could be an effective strategy to rescue the ischemic brain. We investigated whether cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable and potent Ang1 variant, enhances the angiogenesis of human cord blood derived endothelial progenitor cells (hCB-EPCs) for rescuing brain from ischemic injury. COMP-Ang1 markedly improved the tube formation of capillaries by EPCs and incorporation of EPCs into tube formation with human umbilical vein endothelial cells (HUVECs) upon incubation on matrigel in vitro. COMP-Ang1 stimulated the migration of EPCs more than HUVECs in a scratch wound migration assay. The transplanted EPCs and COMP-Ang1 were incorporated into the blood vessels and decreased the infarct volume in the rat ischemic brain. Molecular studies revealed that COMP-Ang1 induced an interaction between Tie2 and FAK, but AKT was separated from the Tie2-FAK-AKT complex in the EPC plasma membrane. Tie2-FAK increased pp38, pSAPK/JNK, and pERK-mediated MAPK activation and interacted with integrins alphanubeta3, alpha4, beta1, finally leading to migration of EPCs. AKT recruited mTOR, SDF-1, and HIF-1alpha to induce angiogenesis. Taken together, it is concluded that COMP-Ang1 potentiates the angiogenesis of EPCs and enhances the vascular morphogenesis indicating that combination of EPCs with COMP-Ang1 may be a potentially effective regimen for ischemic brain injury salvage therapy.


Subject(s)
Animals , Humans , Rats , Angiogenesis Inducing Agents , Blood Vessels , Brain , Brain Injuries , Brain Ischemia , Capillaries , Cartilage Oligomeric Matrix Protein , Cell Membrane , Cell- and Tissue-Based Therapy , Fetal Blood , Human Umbilical Vein Endothelial Cells , Integrins , Ischemia , Morphogenesis , Salvage Therapy , Stem Cells , Wounds and Injuries
6.
Chinese Journal of Medical Genetics ; (6): 322-325, 2013.
Article in Chinese | WPRIM | ID: wpr-237257

ABSTRACT

<p><b>OBJECTIVE</b>To perform mutation analysis for a female with multiple epiphyseal dysplasia (MED) and provide pre-symptomatic and prenatal diagnosis.</p><p><b>METHODS</b>Mutation screening of cartilage oligomeric matrix protein (COMP) gene was carried out through targeted next-generation DNA sequencing and Sanger sequencing.</p><p><b>RESULTS</b>A 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.</p><p><b>CONCLUSION</b>A novel c.956 A>T substitution mutation has been identified in a patient featuring MED.</p>


Subject(s)
Adult , Female , Humans , Base Sequence , Cartilage Oligomeric Matrix Protein , Exons , Extracellular Matrix Proteins , Genetics , Glycoproteins , Genetics , Matrilin Proteins , Mutation , Osteochondrodysplasias , Diagnosis , Genetics , Polymorphism, Single Nucleotide , Sequence Alignment
7.
Chinese Journal of Contemporary Pediatrics ; (12): 937-941, 2013.
Article in Chinese | WPRIM | ID: wpr-345675

ABSTRACT

This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH.


Subject(s)
Child, Preschool , Humans , Male , Achondroplasia , Genetics , Cartilage Oligomeric Matrix Protein , Genetics , Cloning, Molecular , Mutation
8.
Singapore medical journal ; : 702-708, 2013.
Article in English | WPRIM | ID: wpr-337819

ABSTRACT

<p><b>INTRODUCTION</b>To prevent long-term unfavourable consequences to the articular cartilage of weight-bearing joints, serum biomarkers can be used to identify optimum loading of activities. This study aimed to investigate the circulation pattern of serum cartilage biomarkers in healthy adults in response to an uphill walk.</p><p><b>METHODS</b>This study recruited 58 healthy participants for the experimental group and 24 matched participants for the control group. Participants in the experimental group walked continuously for 14 km on a pathway with a 5.97° incline, while participants from the control group walked on a horizontal pathway. Serum was collected from both groups preactivity (i.e. T1), immediately after activity (i.e. T2) and 24 hours after T1 (i.e. T3). The serum cartilage oligomeric matrix protein (COMP), chondroitin sulfate-WF6 (WF6) and hyaluronic acid (HA) levels at each time point were quantified using enzyme-linked immunosorbent assays, and the results analysed.</p><p><b>RESULTS</b>Both groups shared similar demographic characteristics and activity duration. At T2, the serum COMP level of the experimental group was significantly higher than that of the control group, but the serum HA level of the experimental group was significantly lower than that of the control group. No significant difference between the serum WF6 levels of the experimental and control groups was observed at T2.</p><p><b>CONCLUSION</b>Increasing levels of serum COMP demonstrate articular cartilage susceptibility to the increasing load. An unsustainable, high serum COMP level and an undetectable change in WF6 level were considered to be a reversible physiological change of the cartilage. A change in ser um HA level could be related to intensive physical activity and dynamic clearance rather than a change in cartilage structure.</p>


Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Biomarkers , Blood , Cartilage Oligomeric Matrix Protein , Blood , Cartilage, Articular , Metabolism , Chondroitin Sulfates , Blood , Healthy Volunteers , Hyaluronic Acid , Blood , Time Factors , Walking
9.
Chinese Medical Journal ; (24): 1103-1107, 2013.
Article in English | WPRIM | ID: wpr-342231

ABSTRACT

<p><b>BACKGROUND</b>Multiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP).</p><p><b>METHODS</b>Five patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members.</p><p><b>RESULTS</b>We have identified a novel mutation in axon 14 of COMP gene in the family.</p><p><b>CONCLUSIONS</b>This mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.</p>


Subject(s)
Adolescent , Female , Humans , Male , Asian People , Cartilage Oligomeric Matrix Protein , Genetics , Osteochondrodysplasias , Genetics , Pedigree , Point Mutation , Genetics
10.
Journal of Korean Medical Science ; : 725-730, 2013.
Article in English | WPRIM | ID: wpr-80576

ABSTRACT

Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is an angiogenic factor for vascular angiogenesis. The aim was to investigate the effect of an intracavernosal injection of COMP-Ang1 on cavernosal angiogenesis in a diabetic rat model. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats made up the experimental group (1 yr old) and Long-Evans Tokushima Otsuka (LETO) rats made up the control group. The experimental group was divided into vehicle only, 10 microg COMP-Ang1, and 20 microg COMP-Ang1. COMP-Ang1 was injected into the corpus cavernosum of the penis. After 4 weeks, the penile tissues of the rats were obtained for immunohistochemistry and Western blot analysis. The immunoreactivity of PECAM-1 and VEGF was increased in the COMP-Ang1 group compared with the vehicle only group. Moreover, the expression of PECAM-1 and VEGF was notably augmented in the 20 microg Comp Ang-1 group. In the immunoblotting study, the expression of PECAM-1 and VEGF protein was significantly less in the OLEFT rats than in the control LETO rats. However, this expression was restored to control level after intracavernosal injection of COMP-Ang1. These results show that an intracavernosal injection of COMP-Ang1 enhances cavernous angiogenesis by structurally reinforcing the cavernosal endothelium.


Subject(s)
Animals , Male , Rats , Angiopoietin-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Blood Glucose/analysis , Blotting, Western , Body Weight , Cartilage Oligomeric Matrix Protein/genetics , Diabetes Mellitus, Experimental/pathology , Immunohistochemistry , Neovascularization, Physiologic/drug effects , Penis/metabolism , Rats, Long-Evans , Recombinant Fusion Proteins/biosynthesis , Vascular Endothelial Growth Factor A/metabolism
11.
China Journal of Orthopaedics and Traumatology ; (12): 364-368, 2012.
Article in Chinese | WPRIM | ID: wpr-321874

ABSTRACT

<p><b>OBJECTIVE</b>To explore the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis (KOA).</p><p><b>METHODS</b>From 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>WORMS 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.</p>


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Cartilage Oligomeric Matrix Protein , Collagen Type I , Extracellular Matrix Proteins , Glycoproteins , Magnetic Resonance Imaging , Methods , Matrilin Proteins , Osteoarthritis, Knee , Diagnosis , Metabolism , Peptides
12.
China Journal of Orthopaedics and Traumatology ; (12): 380-383, 2012.
Article in Chinese | WPRIM | ID: wpr-321870

ABSTRACT

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>The serum level of COMP can be used as a potential prognostic marker to diagnose KOA.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Biomarkers , Blood , Body Mass Index , Cartilage Oligomeric Matrix Protein , Enzyme-Linked Immunosorbent Assay , Extracellular Matrix Proteins , Blood , Glycoproteins , Blood , Matrilin Proteins , Osteoarthritis, Knee , Blood , Diagnosis
13.
Chinese Medical Journal ; (24): 2181-2184, 2010.
Article in English | WPRIM | ID: wpr-237484

ABSTRACT

<p><b>BACKGROUND</b>Pseudoachondroplasia (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.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>A 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.</p><p><b>CONCLUSIONS</b>Mutations 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.</p>


Subject(s)
Child, Preschool , Female , Humans , Male , Cartilage Oligomeric Matrix Protein , Enzyme-Linked Immunosorbent Assay , Exons , Genetics , Extracellular Matrix Proteins , Blood , Genetics , Glycoproteins , Blood , Genetics , Matrilin Proteins , Mutation , Osteochondrodysplasias , Blood , Genetics , Pedigree , Polymerase Chain Reaction
14.
Acta Physiologica Sinica ; (6): 285-294, 2010.
Article in English | WPRIM | ID: wpr-337747

ABSTRACT

Vascular remodeling is being recognized as a fundamental process during atherosclerosis and restenosis. Cumulative studies have demonstrated that extracellular matrix (ECM) degrading enzymes play a critical role during vascular remodeling. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is a recently identified metalloproteinase family which also has capacity to degrade ECM. ADAMTS family consists of 19 members and has been linked to a variety of physiological processes including development, angiogenesis, coagulation etc. Aberrant expression or function of ADAMTS members have been implicated to many disease states such as arthritis, cancer, thrombocytopenic purpura, but barely described with regard to cardiovascular disease. This review summarizes the recent advance with respect to the role of ADAMTS-7 in vascular remodeling. We review the structure, tissue distribution, substrate, expression and regulation of ADAMTS-7, especially highlight the fine tune by ADAMTS-7 of its substrate cartilage oligomeric matrix protein (COMP) in maintaining vascular homeostasis. By use of rat carotid artery balloon injury model to mimic vascular injury in vivo, we found that ADAMTS-7 protein was accumulated preferentially in neointima and mainly localized in vascular smooth muscle cells (VSMCs). Adenovirus-elicited ADAMTS-7 overexpression greatly accelerated VSMCs migration and proliferation both in vivo and in vitro, and subsequently aggravated neointima thickening post-injury. Conversely, siRNA-mediated ADAMTS-7 knock down bona fide inhibited VSMCs migration and proliferation in cultured VSMCs and injured arteries, and ultimately ameliorated neointima area. Further studies demonstrated that ADAMTS-7 facilitated VSMCs migration through degradation of its substrate COMP. Moreover, we elucidated that COMP has the capacity to maintain the contractile phenotype of VSMCs through interacting with integrin alpha7beta1. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and postangioplasty restenosis.


Subject(s)
Animals , Humans , Rats , ADAM Proteins , Physiology , ADAMTS7 Protein , Atherosclerosis , Carotid Artery Injuries , Metabolism , Pathology , Cartilage Oligomeric Matrix Protein , Cell Movement , Cell Proliferation , Extracellular Matrix Proteins , Metabolism , Physiology , Glycoproteins , Physiology , Matrilin Proteins , Muscle, Smooth, Vascular , Metabolism , Pathology , Tunica Intima , Metabolism , Pathology
15.
China Journal of Orthopaedics and Traumatology ; (12): 959-961, 2010.
Article in Chinese | WPRIM | ID: wpr-344683

ABSTRACT

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.


Subject(s)
Humans , Biomarkers , Blood , Cartilage Oligomeric Matrix Protein , Extracellular Matrix Proteins , Blood , Chemistry , Metabolism , Glycoproteins , Blood , Chemistry , Metabolism , Matrilin Proteins , Osteoarthritis , Blood , Diagnosis , Prognosis
16.
Chinese Journal of Surgery ; (12): 1332-1335, 2009.
Article in Chinese | WPRIM | ID: wpr-299687

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association of matrilin-1 gene polymorphisms with adolescent idiopathic scoliosis (AIS) risk.</p><p><b>METHODS</b>This 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.</p><p><b>RESULTS</b>We 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).</p><p><b>CONCLUSIONS</b>It is concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region is associated with both susceptibility and disease severity in AIS.</p>


Subject(s)
Adolescent , Child , Female , Humans , Male , Young Adult , Cartilage Oligomeric Matrix Protein , Case-Control Studies , Extracellular Matrix Proteins , Genetics , Follow-Up Studies , Genetic Predisposition to Disease , Genotype , Glycoproteins , Genetics , Linkage Disequilibrium , Matrilin Proteins , Polymorphism, Single Nucleotide , Scoliosis , Genetics
17.
Chinese Journal of Surgery ; (12): 1638-1641, 2009.
Article in Chinese | WPRIM | ID: wpr-291041

ABSTRACT

<p><b>OBJECTIVE</b>To determine the circulating matrilin-1 levels in adolescent idiopathic scoliosis (AIS), and to investigate its potential role in etiopathogenisis of AIS.</p><p><b>METHODS</b>This 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.</p><p><b>RESULTS</b>Compared 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.</p><p><b>CONCLUSIONS</b>There 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.</p>


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Cartilage Oligomeric Matrix Protein , Extracellular Matrix Proteins , Blood , Genetics , Follow-Up Studies , Genotype , Glycoproteins , Blood , Genetics , Matrilin Proteins , Scoliosis , Blood , Diagnosis
18.
Chinese Journal of Surgery ; (12): 1728-1731, 2009.
Article in Chinese | WPRIM | ID: wpr-291022

ABSTRACT

<p><b>OBJECTIVES</b>To investigate the association between matrilin-1 gene polymorphism and bracing effectiveness in adolescent idiopathic scoliosis girls.</p><p><b>METHODS</b>In 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.</p><p><b>RESULTS</b>Seventy 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.</p><p><b>CONCLUSIONS</b>Progression 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.</p>


Subject(s)
Adolescent , Child , Female , Humans , Braces , Cartilage Oligomeric Matrix Protein , Extracellular Matrix Proteins , Genetics , Follow-Up Studies , Genotype , Glycoproteins , Genetics , Matrilin Proteins , Polymorphism, Genetic , Prospective Studies , Scoliosis , Genetics , Therapeutics , Treatment Outcome
19.
Chinese Journal of Stomatology ; (12): 551-555, 2008.
Article in Chinese | WPRIM | ID: wpr-251005

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression and localization of cartilage oligomeric matrix protein (COMP), C-X-C motif 9 (CXCL9) and keratin 19 (KRT19) in oral submucous fibrosis (OSF) and to evaluate their roles in the pathopoiesis of OSF.</p><p><b>METHODS</b>The expression and localization of COMP, CXCL9 and KRT19 were investigated in the specimens of 66 patients with oral submucous fibrosis and 14 normal controls by immunohistochemistry, and their protein and mRNA expressions were detected by Western blotting and RT-PCR.</p><p><b>RESULTS</b>COMP was overexpressed in 36 (55%) cases of OSF, and 43 (65%) cases showed positive immunoreactivity for CXCL9 protein in the cytoplasm of inflammatory cells and endothelial cells in OSF. All normal buccal mucosa tissues were stained continuously and strongly for KRT19 in the cytoplasm of basal cells, only 7 (11%) of 66 OSF samples showed faint and fragmented KRT19 staining in the cytoplasm of basal cells. RT-PCR and Western blotting results were fully consistent with the immunohistochemical data.</p><p><b>CONCLUSIONS</b>COMP, CXCL9 and KRT19 play an important role in the pathopoiesis of OSF.</p>


Subject(s)
Adult , Female , Humans , Male , Cartilage Oligomeric Matrix Protein , Chemokine CXCL9 , Metabolism , Extracellular Matrix Proteins , Metabolism , Glycoproteins , Metabolism , Keratin-19 , Metabolism , Matrilin Proteins , Oral Submucous Fibrosis , Metabolism , Pathology
20.
Chinese Journal of Surgery ; (12): 328-331, 2003.
Article in Chinese | WPRIM | ID: wpr-300039

ABSTRACT

<p><b>OBJECTIVES</b>To study cartilage oligomeric matrix protein (COMP) mRNA and protein expression in normal pancreas, chronic pancreatitis (CP), and pancreatic cancer tissues.</p><p><b>METHODS</b>Tissues 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.</p><p><b>RESULTS</b>COMP 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.</p><p><b>CONCLUSION</b>COMP 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.</p>


Subject(s)
Humans , Blotting, Northern , Blotting, Western , Cartilage Oligomeric Matrix Protein , Dimerization , Extracellular Matrix Proteins , Chemistry , Genetics , Metabolism , Glycoproteins , Chemistry , Genetics , Metabolism , Immunohistochemistry , In Situ Hybridization , Matrilin Proteins , Pancreas , Metabolism , Pathology , Pancreatic Neoplasms , Metabolism , Pathology , Pancreatitis, Chronic , Metabolism , Pathology , RNA, Messenger , Genetics , Metabolism
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