keratan-sulfate and Rupture

Genetic variants within genes involved in fibrillogenesis have previously been implicated in anterior cruciate ligament (ACL) injury susceptibility. Proteoglycans also have important functions in fibrillogenesis and maintaining the structural integrity of ligaments. Genes encoding proteoglycans are plausible candidates to be investigated for associations with ACL injury susceptibility; polymorphisms within genes encoding the proteoglycans aggrecan (ACAN), biglycan (BGN), decorin (DCN), fibromodulin (FMOD) and lumican (LUM) were examined.. A case-control genetic association study was conducted. 227 participants with surgically diagnosed ACL ruptures (ACL group) and 234 controls without any history of ACL injury were genotyped for 10 polymorphisms in 5 proteoglycan genes. Inferred haplotypes were constructed for specific regions.. The G allele of ACAN rs1516797 was significantly under-represented in the controls (p=0.024; OR=0.72; 95% CI 0.55 to 0.96) compared with the ACL group. For DCN rs516115, the GG genotype was significantly over-represented in female controls (p=0.015; OR=9.231; 95%CI 1.16 to 73.01) compared with the ACL group and the AA genotype was significantly under-represented in controls (p=0.013; OR=0.33; 95% CI 0.14 to 0.78) compared with the female non-contact ACL injury subgroup. Haplotype analyses implicated regions overlapping ACAN (rs2351491 C>T-rs1042631 T>C-rs1516797 T>G), BGN (rs1126499 C>T-rs1042103 G>A) and LUM-DCN (rs2268578 T>C-rs13312816 A>T-rs516115 A>G) in ACL injury susceptibility.. These independent associations and haplotype analyses suggest that regions within ACAN, BGN, DCN and a region spanning LUM-DCN are associated with ACL injury susceptibility. Taking into account the functions of these genes, it is reasonable to propose that genetic sequence variability within the genes encoding proteoglycans may potentially modulate the ligament fibril properties.

Topics: Adult; Aggrecans; Anterior Cruciate Ligament Injuries; Biglycan; Case-Control Studies; Chondroitin Sulfate Proteoglycans; Decorin; Extracellular Matrix Proteins; Female; Fibrillar Collagens; Fibromodulin; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Keratan Sulfate; Lumican; Male; Polymorphism, Single Nucleotide; Proteoglycans; Risk Factors; Rupture

To evaluate the hypothesis that the concentration of the 1/20/5D4 epitope of keratan sulphate, cartilage oligomeric matrix protein and total sulphated glycosaminoglycans in synovial fluids from dogs with cranial cruciate ligament disease would be affected by tibial plateau levelling osteotomy. In addition, to evaluate the hypothesis that medial meniscal release or meniscal injury would alter the expression of these candidate biomarkers.. Forty-one dogs with naturally occurring cranial cruciate ligament disease were recruited prospectively. Synovial fluids were collected from the index joint before surgery and six weeks and six months postsurgery. Following tibial plateau levelling osteotomy, synovial fluids were assayed for 1/20/5D4 epitope of keratan sulphate and cartilage oligomeric matrix protein concentration using an inhibition ELISA and for sulphated glycosaminoglycans using a direct dye-binding assay.. The sulphated glycosaminoglycans ratio did not change significantly during the study. Medial meniscal injury at entry was associated with lower concentrations of synovial fluid cartilage oligomeric matrix protein (P<0.05, unpaired t test). There was no association between medial meniscal release and the changes in marker concentrations, either from 0 to six weeks or 0 to six months.. Tibial plateau levelling osteotomy did not significantly alter the expression of the named candidate biomarkers. These findings reflect the limited nature of the arthrotomy or indicate that tibial plateau levelling osteotomy does not influence the progression of osteoarthritis (OA). From these studies, there is no evidence that tibial plateau levelling osteotomy affects cartilage metabolism.

Topics: Animals; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Biomarkers; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Glycosaminoglycans; Keratan Sulfate; Male; Osteoarthritis; Osteotomy; Prospective Studies; Rupture; Synovial Fluid; Tibia

Thirty patients had anterior cruciate ligament reconstruction for ongoing instability. Two groups were defined according to gross morphologic features identified during reconstruction: anterior cruciate ligament disruptions with scars attached to a structure in the joint and disruptions without reattachments. Reverse transcription polymerase chain reaction for a subset of extracellular matrix molecules, proteinases, and proteinase inhibitors was done on samples of scarred anterior cruciate ligament tissue removed during reconstructive surgery. Results of the nonattached scar group showed significantly increased mRNA levels for Type I collagen, and an increased Type I to Type III collagen ratio compared with that for the attached scar group. In the first year after injury, decorin mRNA levels in the nonattached scar group also were significantly higher than in the attached scar group. Biglycan mRNA levels in the nonattached scar group correlated closely with Type I collagen mRNA levels. These results suggest differences in cellular expression in torn anterior cruciate ligaments that attach to structures in the joint versus those which do not. Although the molecular mechanisms responsible for these differences have not been delineated, different molecular signals may influence the gross morphologic features of anterior cruciate ligament disruptions or alternatively, differing gross morphologic features may be subject to different mechanical loads leading to altered molecular expression. However, the finding of endogenous cellular activity in injured anterior cruciate ligaments raises the possibility that this activity may be enhanced to improve outcomes.

Topics: Actins; Adolescent; Adult; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Biglycan; Chondroitin Sulfate Proteoglycans; Collagen Type I; Collagen Type III; Decorin; Extracellular Matrix Proteins; Female; Humans; Joint Instability; Keratan Sulfate; Knee Joint; Lumican; Male; Matrix Metalloproteinase 3; Protease Inhibitors; Proteoglycans; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rupture; Tissue Inhibitor of Metalloproteinase-1

To explore the levels of matrix metalloprotease-3 (MMP-3), tissue inhibitor of metalloproteases-1 (TIMP-1), 5D4 keratan sulfate, and two 3B3 chondroitin-sulfate epitopes in several canine osteoarthritic and inflammatory arthropathies.. Blood and synovial fluid were obtained from 103 dogs with rupture of the anterior cruciate ligament (ACLR), osteochondritis dissecans (OCD), fragmented coronoid process (FPC), patella luxation (PL), hip dysplasia (HD) or infectious arthritis. Dogs with non-musculosceletal disorders were used as controls. The biomarkers were measured by immunoassays.. Median levels of synovial MMP-3, TIMP-1 and molar ratios of MMP/TIMP-1 were significantly higher in the arthritis than in the control group. The release of 5D4 keratan sulfate epitope and serum 3B3 neoepitope was reduced in arthritis patients. Increases in synovial TIMP-1 in OA were less pronounced and the molar ratio of MMP-3/TIMP-1 remained far below 1.0, demonstrating a surplus of the protease inhibitor. In osteoarthritic patients median levels of synovial 5D4 keratan sulfate were up-regulated after ACLR and PL and were inversely correlated with increasing duration of lameness. Serum TIMP-1 levels were significantly reduced in the joint disorder group when compared with the control group.. Our observations present the TIMP-1 serum level as a potential marker for the detection of degenerative changes in cartilage and also indicate that in canine OA, the MMP-3 mediated matrix destruction is not of major importance. However MMP-3 seems to be a sensitive marker for the local inflammation in canine arthritis.

Topics: Animals; Anterior Cruciate Ligament Injuries; Arthritis, Infectious; Chondroitin Sulfates; Dogs; Epitopes; Hip Dysplasia, Canine; Keratan Sulfate; Matrix Metalloproteinase 3; Osteoarthritis; Osteochondritis Dissecans; Patella; Rupture; Tissue Inhibitor of Metalloproteinase-1; Ulna Fractures

To investigate longitudinal changes in concentrations of the 1/20/5D4 epitope (5D4) of keratan sulfate and total sulfated glycosaminoglycans (S-GAG) in synovial fluid and serum of dogs with cranial cruciate ligament (CCL) rupture that was repaired via intra-articular surgery.. 58 dogs with a ruptured CCL and osteoarthritis of the affected (index) joint.. Prior to surgical repair of the ruptured CCL, 5D4 concentration was measured in serum and synovial fluid samples by use of an inhibition ELISA, and total S-GAG concentration was measured in synovial fluid samples by use of a direct dye-binding assay. Ruptured CCL were repaired surgically, using an intra-articular fascial graft. Dogs were reexamined 1.5, 7, and 13 months after surgery, and 5D4 and S-GAG concentrations in synovial fluid and serum were measured again.. Serum 5D4 concentrations did not change significantly during the study. Concentrations of 5D4 in synovial fluid (expressed as a ratio of S-GAG concentration) did change significantly with time. In the index joint, the 5D4:S-GAG decreased from 0.19 at the beginning of the study to 0.09 1.5 months after surgery, but 7 months after surgery, the ratio increased again to 0.20.. Results support the hypothesis that serum concentration of 5D4 is not a useful marker of osteoarthritis in dogs. Surgical intervention transiently reduced the concentration of 5D4 in synovial fluid but had no effect on S-GAG concentration.

Topics: Animals; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Biomarkers; Cohort Studies; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Glycosaminoglycans; Joints; Keratan Sulfate; Longitudinal Studies; Male; Osteoarthritis; Rupture; Synovial Fluid

The objective of this study on the glenohumeral joint was to assess the (1) accuracy of clinical diagnosis of osteoarthritis compared with arthroscopic diagnosis, and (2) the ability of biochemical markers in synovial fluid to detect osteoarthritis. Patients (96) were examined clinically and the preoperative diagnosis of osteoarthritis was recorded. At surgery (arthroscopy or arthroplasty), the glenohumeral joint was inspected for signs of osteoarthritis, and the joint osteoarthritis grade (I-IV) was recorded. At surgery, synovial fluid lavage was obtained from the joint, and later analyzed to determine levels of aggrecan components: total sulfated glycosaminoglycan and keratan sulfate epitope, link protein and the chondroitin sulfate epitope recognized by antibody 3B3 (3B3(-)). Compared with arthroscopic diagnosis of osteoarthritis, the results showed that the clinical diagnosis did not wrongly identify joints without osteoarthritis, and was always able to identify joints with advanced (Grade IV) osteoarthritis. Grade II osteoarthritis was rarely identified (10% of the time), and Grade III osteoarthritis was identified 50% of the time. Biochemical assessment of the synovial fluid showed that the catabolic markers (sulfated glycosaminoglycan, keratan sulfate and link protein) were elevated in fluids from joints with moderate (Grade III) and advanced osteoarthritis (Grade IV), and the 3B3(-) epitope was elevated in Grades II, III, and IV. These results show that arthroscopic diagnosis for osteoarthritis, of the glenohumeral joint is particularly useful for early and moderate osteoarthritis, where clinical (nonarthroscopic) diagnosis is poor, and that biochemical analysis of the synovial fluids corresponds well to arthroscopic diagnosis of shoulder osteoarthritis.

Topics: Arthroscopy; Biomarkers; Cross-Sectional Studies; Glycosaminoglycans; Humans; Keratan Sulfate; Osteoarthritis; Predictive Value of Tests; Rotator Cuff Injuries; Rupture; Sensitivity and Specificity; Shoulder Joint; Synovial Fluid