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{L-End}Objective To analyze the local muscle response under continuous ergonomic workload by simulating manual lifting, and to screen the sensitive metabolic biomarkers during fatigue process. {L-End}Methods A total of 13 healthy male volunteers were selected as the study subjects using simple random sampling method. Study subjects underwent repetitive simulated manual lifting for four periods (T1 to T4), each lasting 12 minutes. The degree of work-related fatigue in the forearm, upper arm, shoulder, back, and leg muscles, and the whole body was accessed using Borg 6-20 Rating of Perceived Exertion (RPE) Scale. The venous blood samples were collected from elbow between each two periods to detect the levels of eight metabolic biomarkers: ammonia, lactate, creatine kinase, lactate dehydrogenase (LDH), C-terminal telopeptide of type Ⅰ collagen (CTX-Ⅰ), C-terminal telopeptide of type Ⅱ collagen (CTX-Ⅱ), cartilage oligomeric matrix protein (COMP), and calcium ions. {L-End}Results The RPE scores of the study subjects for the muscles of five body parts and the whole body increased with the increasing lifting periods (all P<0.01). Fatigue was observed in all target muscles, with overall body fatigue occurring in the T2 period. The levels of ammonia, lactate, creatine kinase, LDH, COMP, and calcium ions in the serum of study subjects were higher in the T1 to T4 periods than in the T0 period (all P<0.05). The serum CTX-Ⅰ level was higher in the T1 and T3 periods than that in the T0 period (all P<0.05) , and the serum CTX-Ⅱ level was higher in the T1, T2 and T4 periods than that in the T0 period (all P<0.05). The level of these eight serum metabolic biomarkers fluctuated during the T1 to T4 periods. The serum creatine kinase level increased with the period of lifting (all P<0.05). The serum lactate level was higher in the T3 period than those in the T1 and T2 periods (all P<0.05). The serum LDH and calcium ion levels were higher in the T2 to T4 periods than that in the T1 period (all P<0.05). The serum COMP level was higher in the T2 and T3 periods than that in the T1 period (all P<0.05). Except for CTX-Ⅰ, the levels of other seven metabolic markers in serum were higher in individuals after fatigue than before fatigue (all P<0.05). {L-End}Conclusion Serum metabolic biomarkers such as ammonia, lactate, creatine kinase, calcium ions, LDH, CTX-Ⅱ, and COMP exhibit significant changes before and after fatigue. These metabolic biomarkers could be used as sensitive biomarkers for evaluating muscle fatigue during repetitive works.
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Background:Cartilage oligomeric matrix protein (COMP), is an extracellular matrix (ECM) non-collagenous glycoprotein that is mainly localized within the cartilage, and also be found in tendon and synovium.RecentstudiesinwestandAsiaPacificregionhasshownthatCOMP, is a prognostic marker in Rheumatoid arthritis(RA).Objective:To correlate serum COMP levels with disease severity and cartilage destruction in rheumatoid arthritis.Methods:The study was conducted in Department of Pathology and Rheumatology, Ziauddin University Hospital, Karachi from June 2018 to May 2019. Patients were recruited as per American College of Rheumatology (ACR) 2010 classification criteria. The study populationconsists of 88 healthy subjects and 88 RA patients. Sandwich ELISA technique was used to assess serum COMP level. Other inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) antibodies like rheumatoid factor, and anti-cyclic citrullinated protein (anti-CCP) were also assessed. Results were analyzed using SPSS-20 and P-value ≤0.05 was considered as significant.Results: Serum COMP levels were significantly higher in RA patients 51.35ng/ml than controls 21.454ng/ml with significant p value=<0.0001. There was strong positive correlation between COMP level and disease severity in RA patients with moderate as well as high disease activity score (DAS) with significant p value. Serum COMP showed 96% sensitivity and 83% specificity at level of 27.01ng/ml for diagnosis of RA.Conclusions:COMP has significant positive correlation with severity of RA. Serum COMP can be utilized as a biomarker to quantify cartilage destruction in RA patients
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OBJECTIVE：To investigate the effects of Aconitum injection on cartilage oligomeric matrix protein （COMP）， encoded protein by tumor suppressor gene p53（p53 protein）and bone morphogenetic protein 2（BMP-2）in knee osteoarthritis （KOA）model rabbit ，so as to explore the mechanism of the injection in the treatment of KOA. METHODS ：Totally 24 rabbits were randomly divided into blank group ，model group ，Sodium hyaluronate group and Aconitum injection group ，with 6 rabbits in each group. KOA model was established by injecting 2％ papain-0.03 mol/L L-cysteine solution into the articular cavity of rabbits in model group ，sodium hyaluronate group and Aconitum injection group at the 1st，4th and 7th day ，respectively，except the blank group. At the 1st，4th and 7th day after modeling succeeded ，0.1 mL/kg of normal saline ，Sodium hyaluronate injection and Aconitum injection were injected into the articular cavity of rabbits ，respectively. The cartilage tissue of knee joint was taken from above 4 groups，and the contents of COMP and p 53 protein were detected by ELISA. The cartilage morphology of rabbit knee joint was observed by naked eye. The cartilage of the knee joint was collected and stained by HE staining ，and then the histomorphology changes were observed by light microscope ；Mankin scoring was conducted. The two-step method of PV was used to make the immunohistochemical specimens of knee joint cartilage ，and the relative expression of BMP- 2 was detected. RESULTS ：Compared with blank group ，the edge of cartilage was damaged and the cartilage surface was damaged in the model group. The results of histomorphology observation showed that the joint tissue structure was obviously irregular ，the distribution of chondrocytes was disordered with morphological changes ，and the Mankin score was significantly increased （P＜0.05）；the contents of COMP and cancer cells by indirect inhibition of RAD 51-mediated re - . Suppression of ERCC 1 and RAD51 expression through ERK 1/2 inactivation is essen - tial in emodin-mediated cytotoxicity in human non-small 。E-mail： cell lung cancer cells. p53 protein in knee joint fluid were increased significantly ，while the relative expression of BMP- 2 in knee joint tissue decreased significantly （P＜0.05）. Compared with model group ，the appearance ，histomorphology changes of knee joint cartilage in administration groups were improved，Mankin scores were significantly decreased （P＜0.05）；the contents of COMP and p 53 protein in the knee joint fluid were decreased significantly ，and the relative expression of BMP- 2 in the knee joint tissue were increased significantly （P＜0.05），but there was no significant difference between Aconitum group and Sodium hyaluronate group （P＞0.05）. CONCLUSIONS ：Aconitum injection can improve synovitis inflammation ，delay articular cartilage degeneration ， promote cartilage repair and protect joints of KOA model rabbits. The mechanism may be related to inhibiting COMP secretion ， decreasing p 53 protein expression and promoting BMP- 2 release.
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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.
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Humans , Cartilage Oligomeric Matrix Protein/genetics , Chondromatosis, Synovial , Synovial Membrane , Temporomandibular Joint , Transforming Growth Factor beta3ABSTRACT
Objective To modify CD47 nanobody with the self-folding peptide human cartilage oligomeric matrix protein (COMP48) so as to enhance its affinity to CD47 antigen. Methods The fusion sequences of COMP48 and CD47 nanobody (VHHB1) were designed and synthesized, and the recombinant plasmid pET22b-VHHB1-COMP48 was constructed and transformed into E. coli BL21 (DE3) to induce expression of the fusion protein. The binding specificity and affinity of the fusion protein and the antigen CD47 were detected by Western Blot, indirect enzyme-linked immunosorbent assay (ELISA) and non-competitive ELISA. Results The recombinant VHHB1-COMP48 was expressed in BL21(DE3) by inducing with 1 mmol/L IPTG and purified at 90％homogenous in IMAC. Western Blot results showed that the recombinant protein VHHB1-COMP48 specifically binds to antigen CD47 but not to unrelated protein. The indirect ELISA and non-competitive ELISA results showed that the affinity of the conjugated recombinant protein VHHB1-COMP48 was enhanced compared to that of the non-conjugated nanobody, and the difference was statistically significant ( P<0 . 01 ) . Through non-competitive ELISA , the constants of affinity and dissociation constants were 6.97 ×107 L/mol and 1.434 ×10-8 mol/L, respectively. Conclusions The affinity of the nanobody for the antigen can be improved by conjugating a human cartilage matrix protein (COMP48) after the nanobody.
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Objective This article reported the clinical characteristics and gene mutations of two pseudoachondroplasia cases, and made a literature review in order to improve clinicians' understanding of the disease. Methods Clinical features of two patients who were short stature accompanied with skeletal deformities were summarized, and they accepted whole exome sequencing. We also reviewed literature to summarize the clinical characteristics and known gene research progress of all reported Chinese pseudoachondroplasia cases. Results The two patients' clinical characteristics were short limbdwarfism with skeletal deformity. Genetic results showed that there were two heterozygous mutations in the cartilage oligomeric matrix protein (COMP) gene of the two patients, c.14171419delGAC and c.1552G>A, respectively. Up to March 2019, a total of 58 cases of pseudoachondroplasia have been reported in China. The median height of these patients is-5.03 SDS. The clinical features include abnormal gait, short limbs, short fingers/toes, scoliosis, bracelet sign, ankle sign and other skeletal deformities. COMP is the pathogenic gene and mutations mainly located in calmodulin-like domains. The hotspot mutation is c. 14171419delGAC. Conclusions Pseudoachondroplasia is a kind of rare genetic disease characterized by short stature and skeletal deformities. The clinical and genetic characteristics of the disease were summarized, which may improve the early diagnosis rate.
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Objective@#This article reported the clinical characteristics and gene mutations of two pseudoachondroplasia cases, and made a literature review in order to improve clinicians′ understanding of the disease.@*Methods@#Clinical features of two patients who were short stature accompanied with skeletal deformities were summarized, and they accepted whole exome sequencing. We also reviewed literature to summarize the clinical characteristics and known gene research progress of all reported Chinese pseudoachondroplasia cases.@*Results@#The two patients′ clinical characteristics were short limbdwarfism with skeletal deformity. Genetic results showed that there were two heterozygous mutations in the cartilage oligomeric matrix protein (COMP) gene of the two patients, c. 1417_1419delGAC and c. 1552G>A, respectively. Up to March 2019, a total of 58 cases of pseudoachondroplasia have been reported in China. The median height of these patients is -5.03 SDS. The clinical features include abnormal gait, short limbs, short fingers/toes, scoliosis, bracelet sign, ankle sign and other skeletal deformities. COMP is the pathogenic gene and mutations mainly located in calmodulin-like domains. The hotspot mutation is c. 1417_1419delGAC.@*Conclusions@#Pseudoachondroplasia is a kind of rare genetic disease characterized by short stature and skeletal deformities. The clinical and genetic characteristics of the disease were summarized, which may improve the early diagnosis rate.
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Objective To observe the relationship between serum hydroxyproline,nitric oxide (NO) and cartilage oligomeric matrix protein (COMP) and severity of traumatic osteoarthritis in rats,so as to provide scientific basis for prevention and treatment of Kaschin Beck disease.Methods Thirty-six healthy six-week-old male Wistar rats were divided into 3 groups according to weight via the random digital table method,including control group,ligamentum cutting group,ligamentum cutting + exercise group,with 12 rats in each group.Except the control group,the other two groups of rats were treated by anterior cruciate ligament transaction (ACLT).After 7 days,the ligamentum cutting + exercise group was tested at a 6-animal-treadmills for 20 min per day for 4 weeks.At the tenth week after operation,the surgical unilateral knee joints were taken;under a biological optical microscope,the gross joint morphology of each group was compared,which was scored according to C.Colombo articular cartilage pathological evaluation parameter standard.Rat serum was separated,and the contents of hydroxyproline,NO and COMP were determined.Results There were statistically significant differences among the 3 groups in the pathological evaluation of knee cartilage in rats (F =38.80,P ＜ 0.01).The scores of pathological evaluation of ligamentum cutting group,ligamentum cutting + exercise group were significantly higher than that of the control group (14.82 ± 6.19,18.25 ± 5.71 vs 1.58 ± 0.99,P ＜ 0.01).There was no statistical significant difference in comparison of ligamentum cutting group and ligamentum cutting + exercise group (P ＞ 0.05),and there was no statistical significant difference in serum hydroxyproline content of the 3 groups (F =2.15,P ＞ 0.05).There were statistical significant differences in serum NO and COMP of the 3 groups (F =36.13,16.77,P ＜ 0.01).Conclusions Traumatic osteoarthritis is caused by combining ACLT with movement,and serum levels of NO and COMP are closely related to the severity of osteoarthritis.Detections of NO and COMP are introduced into the research field of Kaschin-Beck disease,which will provide experimental basis for monitoring and treatment of Kaschin-Beck disease.
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Objective To observe the effects of intra-articular injection of sinomenine on morphology of synovium and cartilage as well as contents of MMP-13 and cartilage oligomeric matrix protein(COMP) in serum and synovial fluid of rabbit knee osteoarthritis model.Methods A total of 38 New Zealand white rabbits were randomly divided into 4 groups: control group, model group, hyaluronate group and sinomenine group. Model group, hyaluronate group and sinomenine group established knee osteoarthritis model by intra-articular injection of papain enzyme, and were treated with saline, sodium hyaluronate and sinomenine respectively except for control group. 5 weeks after treatment, all rabbits were sacrificed for HE staining and histological grading on cartilago articularis and synovium, and ELISA method was used to detect the contents of MMP-13 and COMP in rabbit serum and synovial fluid.Results Mankin's scores of articular cartilage and histological scores of synovium in model group were significantly higher than those of control group (P<0.01), and were markedly lower in sinomenine group than those of model group (P<0.01); the contents of MMP-13 and COMP in serum and synovial fluid of model group were significantly raised compared with control group (P<0.01), and were reduced obviously in sinomenine group compared with model group (P<0.05,P<0.01).Conclusion Intra-articular injection of sinomenine can reduce the levels of MMP-13 and COMP in serum and synovial fluid of rabbit knee osteoarthritis model, and improve synovial inflammation, as well as delay the degradation of articular cartilage.
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Objective To investigate cartilage oligomeric matrix protein( COMP) gene mutation in a three-generation pedigree with two cases of pseudoachondroplasia, and to definitize genotype-phenotype correlation. Methods The clinical data and peripheral blood were collected from the patients with pseudoachondroplasia and their family members. All the 19 exons and their flanking sequences of COMP gene in two patients and three unaffected family numbers and 50 unrelated individuals were analyzed by PCR amplification and direct sequencing. Results The proband, a 6-year-old girl presented with typical clinical features of pseudoachondroplasia, including disproportionate short limb dwarfism, staggering gait, double genu varus deformity, and wider clinical and imaging long bone metaphysis. The 33-year-old father showed a similar manifestation including disproportionate short limb dwarfism and double genu varus deformity, and was performed correcting operation on lower limbs for double genu varus at the age of 10 years. DNA sequencing analysis of the COMP gene revealed a del mutation ( c. 1417 1419delGAC)in exon 13 in two patients with pseudoachondroplasia, but not in the other unaffected members from the pedrgree and 50 control subjects. Conclusion A del mutation c. 1417 1419delGAC of COMP gene may contribute to the disease in the pedigree.
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Objective To detect the COMP and aggrecan content in serum of patients with KOA and explore its correlative factors.Methods COMP and aggrecan in serum of 100 patients with knee-osteoarthritis(KOA group)and 30 healthy volunteers (control group)were measured by ELISA.Correlative factors for COMP and aggrecan levels were tested by linear regression analy-sis.Results COMP and aggrecan levels in KOA group were significantly higher than that in control group (P < 0.05 ).Serum COMP and aggrecan levels were positively correlated with age,body mass index(BMI),WOMAC scores and X-ray K-L grade(P <0.05).Conclusion Serum COMP and aggrecan are useful markers in the diagnosis,which their level in KOA are higher than the normal people.Moreover,these rise of levels positively correlated with clinical disease parameters and radiological joint damage.
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Objective:To identify the epitope of mAb15A11 which is specific against RA associated autoantigen cartilage oligomeric matrix protein ( COMP ).Methods: A filamentous phage library displaying random linear dodecapeptides was used to mapping the epitope of mAb15A11.After three rounds of screenings,40 phage clones were selected at random and sequenced.The specificity of phages was confirmed by enzyme immunoassays.Homology search by ClustalW2 and structure analysis by PyMol to identified the epitope amino acid sequence.Western blot analysis of COMP and ELISA analysis of COMP-derived peptides were used to confirm epitope′s characterization.Results: After repeated screenings using bio-panning method, 2 clones were identified, which interacted specifically with mAb 15A11.Homology search did not find succession consensus sequence within COMP molecular,which indicated that the epitope was not linear.PyMol Structure analysis identified the rationality of conformational epitope.Western blot analysis and ELISA of EDTA-treated COMP further prove an conformational structure of the epitope recognized by mAb 15A11.ELISA analysis of COMP-derived peptides demonstrated both disulfide bonds between 229 C-243 C and 237 C-253 C and every epitope amino acid of 232 G,238 H,240 H,241 A,244 V,247 R and 251 R were essential to the binding of mAb 15A11 with COMP.Conclusion: In this study, the potential B cell antigentic epitopes of mAb 15A11 was identified by phage display library.The epitope amino acids sequence and char-acterization were also recognized.It may have important theoretical value for the study of reaction mechanism of COMP antibody and antigen and may also show application significance in the detection of rheumatoid arthritis.
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By observing the arthroscopy cleaning technique with postoperative oral administration with reinforcing kidney and activating blood Chinese herbal medicine in the treatment of knee osteoarthritis (KOA), this article was aimed to evaluate the clinical curative effect and its influence on serum C endⅡ collagen type (CTX-Ⅱ) and cartilage oligomeric matrix protein (COMP). Patients who met the diagnostic criteria were randomly divided into the treatment group and control group, with 30 cases in each group. Joint limited debridement was firstly applied. And the degree of articular cartilage degeneration, synovial hyperplasia and inflammatory degree were observed and recorded. Preoperative venous blood was collected. The contents of CTX-Ⅱ and COMP were detected with ELISA method. After surgery, in the treatment group, surgery plus postoperative oral administration with reinforcing kidney and activating blood Chinese herbal medicine was given. In the control group, surgery plus oral administration with celecoxib capsules was given. Four weeks before and after the treatment, the WOMAC knee function score was used in the evaluation of clinical curative effect. The contents of postoperative serum CTX-Ⅱ and COMP were determined. The results showed that the effectiveness of the treatment group was higher than that of the control group (P < 0.05). In the treatment group, the WOMAC score in pain, rigidity, difficulty of activity and total score had significant differences compared with the control group (P < 0.05). There were statistical significances on serum CTX-Ⅱ and COMP in the treatment group before and after the treatment, as well as the comparison between the treatment and control group both before and after the treatment (P < 0.05). Serum CTX-Ⅱ and COMP had positive correlation with the degeneration of cartilage and synovial hyperplasia with statistical significances (P < 0.05). It was concluded that joint limited debridement under arthroscopy combined with reinforcing kidney and activating blood method had synergistic effect in the treatment of KOA. It can effectively relieve the clinical symptoms and improve the knee joint function. It can also obviously reduce the contents of serum CTX-Ⅱ and COMP. There was internal close relation between the articular cartilage degeneration, synovial hyperplasia under the arthroscopy in KOA and cytokines of CTX-Ⅱ and COMP. The cytokines of CTX-Ⅱ and COMP provided important references for the estimation of articular cartilage degeneration and synovial hyperplasia.
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Objective To explore the effect of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein injection (rhTNFR:FC) on the expression of cartilage oligomeric matrix protein (COMP) in the synovial fluid and peripheral blood of juvenile idiopathic arthritis (JIA); and to explore the clinical significance of COMP for JIA and the relationship between rhTNFR:FC and COMP in JIA.Methods Thirty-five patients with JIA (JIA group),30 patients with traumatic arthritis (trauma group) and 30 patients with indirect inguinal hernia hernioplasty (normal group) were included.Peripheral blood from all enrolled patients and synovial fluid from 15 JIA and 10 trauma arthritis were obtained for COMP detection before the treatment.Fifteen JIA (group A) patients were treated with combined rhTNFR:FC,diseasemodifying antirheumatic drugs (DMARDs) and non-steroid anti-inflammatory drugs (NSAIDs),20 JIA (group B) were treated with combined DMARDs and NSAIDs.After three to six months' treatment and when the disease were in remission,peripheral blood from group A and B were drawn for COMP detection.In group A,the synovial fluid from 5 patients were obtained for COMP detection after treatment.At the same time,such as tender joint count (TJC),swollen joint count (SJC),time for morning stiffness,blood routine,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) and other parameters before and after treatment were measured.The level of COMP was tested by double antibody sandwich enzyme-linked immunosorbent assay.The measurement data were tested for variance and independent sample t-test; and the enumeration data were tested by chi-squared or Fisher's exact test.Pearson's correlation analysis was adopted to analyze the association among the variables.Results ① The blood COMP level before treatment was (0.77±0.29) ng/ml in the JIA group,(1.00±0.28) ng/ml in the traumatic arthritis group,and (1.33±0.37) ng/ml in the normal control group.The level in the former two groups was obviously lower than that in the normal control group.The variation was statistically significant (F=25.345,P＜0.05).The comparison between any two groups was statistically significant (P＜0.05).② The COMP level in the synovial fluid before treatment were (14.8±1.6) ng/ml in the JIA group,(15.1±1.0) ng/ml in the traumatic arthritis group.The variation was not stati-stically significant (t=0.523,P=0.606).③ The serum COMP level of the systemic JIA group was obviously lower than that of the oligoarticular JIA patients,and patients with enthesitis-related arthritis and polyarticular JIA (0.26± 0.03 vs.0.87±0.17,0.89±0.22 and 0.70±0.35 ng/ml,respectively; F=9.244,P＜0.05).④ The serum COMP level of JIA at the acute phase was negatively correlated with white blood cells count (WBC),CRP and ESR (r=-0.556,-0.582 and-0.684,respectively; P all＜0.05).By contrast,no correlation was detected between the serum COMP level and joint tenderness index,joint swelling index,morning stiffness duration,hemoglobin level and platelet count(r=0.06,-0.206,-0.107,0.15 and-0.185,respectively; P all ＞0.05).⑤ The serum COMP level was obviously lower in the JIA with joint destruction than that without joint destruction (0.52±0.22 vs.0.92±0.22 ng/ml; t=5.207,P＜0.05).⑥After treatment,the blood COMP level in group A was (1.33±0.21) ng/ml and (0.96±0.22) ng/ml in group B,which was obviously higher than that in the JIA group before treatment (0.77±0.29) ng/ml.In addition,the level in group A was higher than that in group B.The variation was statistically significant (F=24.681,P＜0.05).⑦ After treatment,the COMP level in the synovial fluid (18.4± 1.1) ng/ml (n=5) was higher than that before the treatment was (14.8± 1.6) ng/ml (n =15).The variation was of statistical significant (t=4.565,P＜0.05).Conclusion The COMP level in blood and synovial fluid declines before treatment and increases after treatment.The increase is more obvious after combined with rhTNFR:FC treatment.The serum COMP level is remarkably decreased in JIA at the acute phase,systemic JIA,and the JIA with destruction of joint,and showes a negative correlation with WBC,CRP and ESR.Serum COMP may be a useful marker of active disease,destruction of joint and growth inhibition for patients with JIA.rhTNFR:FC treatment for JIA can facilitate the recovery of COMP.
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Objective To investigate the level of serum cartilage oligomeric matrix protein (COMP) and its relationship with vascular calcification in diabetic nephropathy (DN) patients .Methods COMP was tested in 54 (DN) group and 28 matched healthy persons (healthy group) .DN group was divided into vascular calcification group (VC) and non‐vascular calcification (non VC) group .DN group was also divided into cardiovascular disease group (CVD‐y) and without cardiovascular disease group (CVD‐n) in view of the company of cardiovascular disease .Serum COMP levels was compared between the DN group and the control group ,the VS group and the non VS group ,and the CVD‐y group and the CVD‐n group .The correlations between COMP level and the occur‐rence of cardiovascular disease ,the incidence of vascular calcification were estimated by Wald analysis of the application of Wald test .Results Serum COMP in DN group was significantly higher than the control group;Aortic arch calcification accounted for 75 .9% of the DN group .The serum COMP in VC group was higher than that of non VC group ,CVD‐y group had higher COMP than CVD‐n group old respectively with every 10 ng/mL increased in concentration of serum COMP .Conclusion The higher of concentration of serum COM P ,the more risk of vascular calcification and CVD .
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BACKGROUND: Estrogens act on estrogen receptors distributed in articular cartilages, synovial membrane, and ligaments, which are thought to be related with degenerative changes. Meanwhile, progesterone is known to have a weak anabolic action on bone formation This study evaluates the effects of estrogen and progesterone hormone on bone/cartilage turnover in ovariectomized (OVX) rats. METHODS: Thirty-five 7-month-old female Sprague-Dawley rats were randomly divided into 5 groups and then ovariectomized bilaterally except the sham control group. The first and the second group acting as controls did not receive hormonal therapy, the third group received estrogen, the fourth group received progesterone, and the fifth group received combination of both hormones 10 weeks after surgery. Evaluations were done using the serum levels of cartilage oligomeric matrix protein (COMP) for cartilage turnover, collagen type I C-telopeptide (CTX-1) and osteocalcin (OC) for bone turnover at 11, 15, 19 weeks after OVX and histology using the Osteoarthritis Research Society International (OARSI) osteoarthritis (OA) cartilage histopathology assessment system. RESULTS: Significantly less cartilage degradation (decreased levels of COMP) was found in the combined hormone treated group in comparison with OVX group. Similarly, both hormonal treatment resulted in increased bone formation and decreased bone resorption i.e., a low overall bone turnover status (decrease in the serum OC and CTX-1 levels). CONCLUSIONS: Combined estrogen and progesterone therapy was found to be convincing in terms of reducing the severity of OA in this experimental model.
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Animals , Female , Rats , Biomarkers/blood , Bone Remodeling/drug effects , Bone and Bones/chemistry , Cartilage/chemistry , Collagen Type I/blood , Disease Models, Animal , Estrogens/pharmacology , Extracellular Matrix Proteins/blood , Glycoproteins/blood , Histocytochemistry , Hormone Replacement Therapy/methods , Osteoarthritis/blood , Osteocalcin/blood , Ovariectomy , Progesterone/pharmacology , Rats, Sprague-DawleyABSTRACT
Objective To study the diagnostic value of cartilage oligomeric matrix protein for early cartilage destruction in osteoarthritis and assess its value in the prediction of the disease progression.Methods The osteoarthritis animal models were developed by immobilizing the right knees of 18 rabbits in full extension position using plaster East.Knee joint pathological changes at week 2 and 6 were examined for pathological severity evaluation of osteoarthritis.ELISA sandwich method was used to measure the levels of cartilage oligomeric matrix protein(COMP) in serum before and after modeling(at week 2 and 6 respectively) and immunohistolgy method was used to examine the levels of COMP in knee articular cartilage of osteoarthritis animal models.Correlation analysis was performed to demonstrate the relationship between the levels of COMP in the serum and the pathological severity of osteoarthritis.Pearson's test and t-test were used for correlation analysis.Results ①) Osteoarthritis animal models could be successfully developed by immobilizing the right knees of rabbits in full extension position using plaster east for 2 weeks.Early histopathological changes in the articular cartilage could be observed,At week 6,the typical histopathological characteristics could be seen.②With the extension of modeling time,serum COMP levels persistently increased.The serum COMP levels before modeling,at modeling week 2,week 6 were (3.35±0.20),(3.64±0.18),(3.96±0.44) μg/L respectively,the difference was significant (P＜0.05).③ The level of COMP in the articular cartilage of non-osteoarthritis animal models,models at week 2,week 6 were (2.7±1.8 )％ ,(5.7±0.7)％,(7.6±0.7)％ respectively (P＜0.05 for all).④ The level of COMP in the serum was linearily correlated with the pathological severity of osteoarthritis(r＞0.770 for all,and P＜0.05 for all).Conclusion Levels of COMP in the serum can help to make early diagnosis of osteoarthritis,and elevated COMP level can predict the progression of osteoarthritis.
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Objectiye To study the levels of cartilage oligomeric matrixprotein (COMP) and matrix metalloproteinase-3 (MMP-3) in the serum fluid of osteoarthritic rabbit models and their relationships with the severity of pathological changes, so as to investigate their correlation with osteoarthritis(OA). Methods The osteoarthritic animal models were get from immobilizing the right knees of 18 rabbits in full extension using plaster cast. Knee joint pathological changes of 2,6 weeks were examined for pathological severity of OA; ELISA sandwich method was used to measure the levels of COMP and MMP-3 in serum before and after modeling( at 2, 6 weeks respectively); X ray of model keens was also obtained in different period.Correlation analysis was performed to demonstrate the relationship between the levels of COMP, MMP-3 in the serum and the pathological severity of OA. Results ( 1 ) Morphological observations: immobilizing the right knees of rabbits in full extension using plaster cast was a reliable methed for osteoarthritic animal models and the typical histopathologic character was seen; the severity of osteoarthritisgradually increased with time extended. (2) The levels of COMP[(3.64 ±0. 18)μg/L], MMP-3 [(1.99 ±0. 81 ) μg/L]in the serum of 2 weeks osteoarthritic animal models were higher than those before immobilizing with plaster cast [COMP(3.35 ±0. 20) μg/L,MMP-3( 1.61 ±0. 71 ) μg/L]. The levels of COMP[(3.96 ±0. 44) μg/L],MMP-3[(3.44 ±0. 91) μg/L] of 6 weeks were much higher,with a significant difference(P ＜0.05). The levels of COMP, MMP-3 in serum had a linear correlation with the pathological severity of OA (r ＞0. 710,and P ＜ 0. 05 ). Conclusion The levels of COMP and MMP-3 in serum can help to predict and evaluate the progression of OA.
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Objective To compare the effect of ibuprofen and glucosamine on synoviocyte proliferation and cartilage oligomeric matrix protein (COMP) expression in human knee osteoarthritis. Methods Human synoviocytes were isolated from synovium (earlier stage and late stage of OA) by tissue culture and were cocultured with ibuprofen and glucosamine. The concentration of COMP was determined by MTS/PMS method and hCOMP kit. Two-tailed t-test was used for statistical analysis. Results The observation time of tissue culture was determined at 5～7 day by the MTS/PMS method. The A values of glucosamine [ late stage group (0.054±0.021), early stage group (0.777±0.034)] were less than the normal serum control group (P＜0.05).Both ibuprofen [late stage group (35.4±1.9), early stage group (46.0±2.2)] and glucosamine [late stagegroup (36.6±1.3), early stage group (48.8±1.3) ] could decrease the concentration of COMP in synoviocyte secretion in vitro (P＜0.05). Conclusion Glucosamine can inhibit the synoviocyte proliferation of human knee osteoarthritis (both early stage and late stage) in vitro. Both ibuprofen and glucosamine can inhibit the COMP secretion of synoviocyte in vitro.
ABSTRACT
Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous chondroplasia, characterized by delayed development of the ossification centers and, deformities of the extremities that involve only the epiphysis and result in mild short stature. Mutations in the cartilage oligomeric matrix protein (COMP) gene are most commonly found, and most of the mutations are located in the calmodulin-like repeats and the C-terminal domain. We report a Korean kindred of?12 family members with MED in four generations who were found to have a novel mutation in the COMP gene. A pedigree showed early onset osteoarthritis requiring arthroplasty that was an autosomal dominant inherited trait. Radiological examinations demonstrated the presence of osteochondral defects in the medial femoral condyles, and the knee and hip joints showed variable degrees of precocious degenerative changes. Mutation analysis of the COMP gene in the proband and five other affected family members identified a novel missense mutation, c.1280G>C (p.Gly427Ala) in exon 12, which was not found in three unaffected family members. Direct sequencing of the COMP gene may yield pathogenic mutations in dominantly inherited MED cases, and may provide opportunities of carrier detection among high-risk family members, leading to genetic counseling for early diagnosis and intervention before the onset of complications.