OBJECTIVE: To analyze the differences in the effects of different mechanical stimuli on cells, cytokines, and proteins in synovial fluid of osteoarthritis joints, and to elucidate the indirect mechanism by which mechanical signals remodel the synovial fluid microenvironment through tissue cells. METHODS: Systematically integrate recent literature, focusing on the regulatory effects of different mechanical stimuli on the physicochemical properties of synovial fluid. Analyze the dynamic process by which mechanical stimuli regulate secretory and metabolic activities through tissue cells, thereby altering the physicochemical properties of cytokines and proteins. RESULTS: Appropriate mechanical stimuli activate mechanical signals in chondrocytes, macrophages, and synovial cells, thereby influencing cellular metabolic activities, including inhibiting the release of pro-inflammatory factors and promoting the secretion of anti-inflammatory factors, and regulating the expression of matrix and inflammation-related proteins such as cartilage oligomeric matrix protein, peptidoglycan recognition protein 4, and matrix metalloproteinases. CONCLUSION Mechanical stimuli act on tissue cells, indirectly reshaping the synovial fluid microenvironment through metabolic activities, thereby regulating the pathological process of osteoarthritis.
Humans ; Osteoarthritis/physiopathology* ; Synovial Fluid/chemistry* ; Chondrocytes/metabolism* ; Cytokines/metabolism* ; Macrophages/metabolism* ; Stress, Mechanical ; Cartilage Oligomeric Matrix Protein/metabolism* ; Matrix Metalloproteinases/metabolism* ; Synovial Membrane/cytology*

Abnormal accumulation of collagen fibrils is a hallmark feature of oral submucous fibrosis (OSF). However, the precise characteristics and underlying mechanisms remain unclear, impeding the advancement of potential therapeutic approaches. Here, we observed that collagen I, the main component of the extracellular matrix, first accumulated in the lamina propria and subsequently in the submucosa of OSF specimens as the disease progressed. Using RNA-seq and Immunofluorescence in OSF specimens, we screened the cartilage oligomeric matrix protein (COMP) responsible for the abnormal collagen accumulation. Genetic COMP deficiency reduced arecoline-stimulated collagen I deposition significantly in vivo. In comparison, both COMP and collagen I were upregulated under arecoline stimulation in wild-type mice. Human oral buccal mucosal fibroblasts (hBMFs) also exhibited increased secretion of COMP and collagen I after stimulation in vitro. COMP knockdown in hBMFs downregulates arecoline-stimulated collagen I secretion. We further demonstrated that hBMFs present heterogeneous responses to arecoline stimulation, of which COMP-positive fibroblasts secrete more collagen I. Since COMP is a molecular bridge with Fibril-associated collagens with Interrupted Triple helices (FACIT) in the collagen network, we further screened and identified collagen XIV, a FACIT member, co-localizing with both COMP and collagen I. Collagen XIV expression increased under arecoline stimulation in wild-type mice, whereas it was hardly expressed in the Comp^-/- mice, even with under stimulation. In summary, we found that COMP may mediates abnormal collagen I deposition by functions with collagen XIV during the progression of OSF, suggesting its potential to be targeted in treating OSF.
Oral Submucous Fibrosis/pathology* ; Cartilage Oligomeric Matrix Protein/genetics* ; Animals ; Mice ; Humans ; Fibroblasts/metabolism* ; Collagen Type I/metabolism* ; Arecoline/pharmacology* ; Mouth Mucosa/metabolism* ; Cells, Cultured ; Fluorescent Antibody Technique

INTRODUCTIONTo 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.

METHODSThis 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.

RESULTSBoth 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.

CONCLUSIONIncreasing 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.

Adolescent ; Adult ; Biomarkers ; blood ; Cartilage Oligomeric Matrix Protein ; blood ; Cartilage, Articular ; metabolism ; Chondroitin Sulfates ; blood ; Female ; Healthy Volunteers ; Humans ; Hyaluronic Acid ; blood ; Male ; Time Factors ; Walking ; Young Adult

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.
Angiopoietin-1/genetics/*metabolism ; Animals ; Antigens, CD31/metabolism ; Blood Glucose/analysis ; Blotting, Western ; Body Weight ; Cartilage Oligomeric Matrix Protein/genetics/*metabolism ; Diabetes Mellitus, Experimental/*pathology ; Immunohistochemistry ; Male ; Neovascularization, Physiologic/*drug effects ; Penis/metabolism/pathology ; Rats ; Rats, Long-Evans ; Recombinant Fusion Proteins/biosynthesis/genetics/*pharmacology ; Vascular Endothelial Growth Factor A/metabolism

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

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.
ADAM Proteins ; physiology ; ADAMTS7 Protein ; Animals ; Atherosclerosis ; physiopathology ; Carotid Artery Injuries ; metabolism ; pathology ; Cartilage Oligomeric Matrix Protein ; Cell Movement ; Cell Proliferation ; Extracellular Matrix Proteins ; metabolism ; physiology ; Glycoproteins ; physiology ; Humans ; Matrilin Proteins ; Muscle, Smooth, Vascular ; metabolism ; pathology ; Rats ; Tunica Intima ; metabolism ; pathology

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

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