The relationship between parafunctional masticatory activity and arthroscopically diagnosed temporomandibular joint pathology.

PURPOSE: The purpose of this investigation was to assess the relationship between parafunctional masticatory activity and arthroscopically visualized changes in patients with severe, unremitting symptoms caused by intra-articular temporomandibular joint pathology. The working hypothesis was that the presence of parafunctional activity leads to increased arthroscopically diagnosed pathology. MATERIALS AND METHODS: Temporomandibular joint arthroscopy was performed on 124 joints in 83 patients (female:male, 5.4:1; mean age, 35 years; mean duration of symptoms, 49 months) with severe symptoms unresponsive to nonsurgical management. Preoperatively, the presence of parafunctional habits (bruxism, clenching) was assessed, and joints were classified as either with or without parafunctional influences. Joints were diagnosed arthroscopically and assessed for the presence or absence of osteoarthritis, synovitis, and adhesions. Analyses were performed to determine significant relationships between parafunctional activity and the presence of osteoarthritis, synovitis, and adhesions. RESULTS: Parafunctional influences were present in 82 of 124 joints (66%). Clinically diagnosed osteoarthritis was present in 59 of 124 joints (48%) and arthroscopically diagnosed osteoarthritis was seen in 82 of 124 joints (66%). Arthroscopically, synovitis was diagnosed in 123 of 124 joints (99%) and adhesions in 93 of 124 joints (75%). Statistical analyses showed a significant relationship between parafunction and clinically diagnosed osteoarthritis, and suggested a close relationship between parafunction and arthroscopically diagnosed osteoarthritis. A significant association between clinically and arthroscopically diagnosed osteoarthritis and adhesions was also demonstrated. There also was no significant relationship detected between parafunction and the presence of synovitis or adhesions seen arthroscopically. CONCLUSIONS: It was concluded that parafunctional masticatory activity and its influence on joint loading contribute to osteoarthritis of the temporomandibular joint. Such osteoarthritis is associated with adhesions of the joint. Arthroscopically diagnosed synovitis is not specifically associated with parafunction, and it appears that numerous other causative factors may contribute to its development in the TMJ. Because abnormal joint loading is a major causative factor in cartilage degradation, biochemical and biomechanical abnormalities, and intraarticular temporomandibular pathology, clinicians must identify and address parafunctional masticatory activity during nonsurgical, surgical, and postsurgical treatment regimens.

Osteoarthritis and synovitis as major pathoses of the temporomandibular joint: comparison of clinical diagnosis with arthroscopic morphology.

PURPOSE: The purposes of this investigation were to determine how common osteoarthritis and synovitis are in patients with severe, recalcitrant temporomandibular joint (TMJ) symptoms using clinical diagnostic criteria as well as arthroscopic examination, and to compare the accuracy of the clinical and arthroscopic diagnoses with respect to specificity and sensitivity. PATIENTS AND METHODS: Clinical and arthroscopic diagnoses were established in 126 joints of 84 patients with severe TMJ symptoms recalcitrant to conservative therapy. All joints were classified as having osteoarthritis (OA) or no osteoarthritis (non-OA) and synovitis (syn) or no synovitis (non-syn) using clinical and arthroscopic criteria. Chi-squared analysis was used to determine whether there was a relationship between the clinical and arthroscopic diagnoses. Preoperative clinical diagnoses were compared with arthroscopic morphologic diagnoses to determine the specificity and sensitivity of the clinical diagnostic criteria for synovitis and osteoarthritis. RESULTS: A preoperative clinical diagnosis of OA was established in 59 of 126 joints (47%) compared with an arthroscopic diagnoses of OA in 82 of 126 joints (65%). Chi-squared analysis showed a significant relationship between the clinical and arthroscopic diagnosis of OA. A clinical diagnosis of OA was associated with a high specificity (.977); however, there were 23 of 82 (.293) false-negative findings and a sensitivity of only .707. A preoperative clinical diagnosis of synovitis was established in 114 of 126 joints (90%), compared with an arthroscopic diagnosis of synovitis in 112 of 126 (89%). Chi-squared analysis did not show a significant relationship between the clinical and arthroscopic diagnosis of synovitis. A clinical diagnosis of synovitis was associated with a high sensitivity (.920); however, there were 11 of 14 false-positive findings (.786) associated with a low specificity (.214). CONCLUSIONS: Although there was high specificity for the clinical diagnosis of OA, the sensitivity was very low. (Comparison of clinical and arthroscopic diagnoses showed that osteoarthritis frequently escapes clinical detection. The clinical diagnosis of synovitis showed that low specificity and symptoms may be caused by other pathoses.

Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression.

The effects of short- and long-term load-controlled compression on the levels of aggrecan mRNA have been determined. Results show that a compressive stress of 0.1 MPa on bovine articular cartilage explants for 1, 4, 12, and 24 h produces a transient up-regulation of aggrecan mRNA synthesis. At 1 h, aggrecan mRNA levels in loaded explants were increased 3.2-fold compared to control explants. At longer times (>/=4 h), the levels of aggrecan mRNA returned to baseline values or stayed slightly higher. There is a dose dependence in the response of the explant to increasing levels of compressive stress (0-0.5 MPa) for 1 h. Aggrecan mRNA levels increased 2- to 3-fold at 0-0.25 MPa. At 0.5 MPa, the level of aggrecan mRNA was lower than those at 0.1 and 0.25 MPa. This dose-dependent effect suggests a reversal of the stimulatory effects of compression on aggrecan gene expression at higher loads. After 24 h of compression, the levels of aggrecan mRNA in explants subjected to any of the stress levels were not significantly different from those in control explants. The stimulatory effect of 0.1 MPa compressive stress on aggrecan mRNA levels was blocked by Rp-cAMP and U-73122, indicating the involvement of the classical signal transduction pathways in the mechanical modulation of aggrecan gene expression. The responses of link protein mRNA to compression paralleled those of aggrecan, while there was no significant change in expression of the gene for the housekeeping protein elongation factor-1 alpha. The results indicate that articular cartilage chondrocytes can respond to short-term compressive loads by transiently up-regulating expression of the aggrecan gene. The fact that long-term compression did not significantly alter aggrecan mRNA levels suggests that previously observed inhibitory effects of prolonged static compression on proteoglycan synthesis in articular cartilage may be, for the most part, mediated through mechanisms other than suppression of aggrecan mRNA levels.

Proteoglycans in the synovial fluid of the temporomandibular joint as an indicator of changes in cartilage metabolism during primary and secondary osteoarthritis.

PURPOSE: The specific aim of this investigation was to assess differences between primary and secondary osteoarthritis (OA) of the temporomandibular joint (TMJ) using clinical evaluation and synovial fluid analysis for proteoglycans. MATERIALS AND METHODS: Arthroscopic surgery was performed on 101 TMJs from patients with significant pain or dysfunction and who had failed to respond to treatment. Joints were assessed for primary and secondary osteoarthritis. Synovial fluid aspirates were obtained and analyzed to determine the levels of keratan sulfate (KS) epitope and a novel 3B3(-) epitope by enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty-four patients and 67 joints had OA diagnosed by both clinical examination and arthroscopy. Primary OA was diagnosed in 14 joints (20%), and the remaining 53 joints were regarded as having secondary OA. No differences were detected in the levels of KS in the synovial fluid from the primary and secondary OA joints. Furthermore, the 3B3(-) epitope was not detectable in the synovial fluid aspirates of any TMJ. CONCLUSION: Secondary OA is a common disorder of the TMJ. However, there is no apparent difference in the metabolism of the joints with primary and secondary OA as assessed by proteoglycans in the synovial fluid. The apparent absence of the 3b3(-) epitope, in contrast to its presence in OA of other major synovial joints, suggests that there are some differences between the cartilage metabolism of the TMJ and these other joints during OA.

Correlation between arthroscopic diagnosis of osteoarthritis and synovitis of the human temporomandibular joint and keratan sulfate levels in the synovial fluid.

PURPOSE: The specific aims of this investigation were to determine if there is a relationship between an arthroscopic diagnosis of synovitis and osteoarthritis, and if the presence of synovitis influences the level of cartilage degradation, as evidenced by keratan sulfate levels in the synovial fluid. PATIENTS AND METHODS: Arthroscopic surgery was performed on 114 temporomandibular joints in 88 patients who had significant pain or dysfunction and whose condition had failed to improve with conservative treatment. Synovial fluid aspirates were obtained immediately before arthroscopy and used for the determination of keratan sulfate levels. Arthroscopic examination included assessment of the presence or absence of osteoarthritis and synovitis. RESULTS: Synovitis was present in 90% of joints, and osteoarthritis was present in 62% of joints examined arthroscopically. Both osteoarthritis and synovitis existed in 57% of the joints. Joints with an arthroscopic diagnosis of synovitis had significantly lower levels of keratan sulfate in the synovial fluid aspirates than joints with osteoarthritis. Synovial fluid aspirates from temporomandibular joints with osteoarthritis had significantly higher levels of keratan sulfate than synovial fluids from joints without osteoarthritis. CONCLUSIONS: Osteoarthritis and synovitis are common diagnoses and are often present concurrently in patients with symptomatic temporomandibular joints. Osteoarthritis is associated with elevated keratan sulfate levels; however, the elevation of keratan sulfate is less in patients with concomitant synovitis.

Biochemical markers in synovial fluid identify early osteoarthritis of the glenohumeral joint.

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.

Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse.

The levels of proteoglycan aggregate components (link protein, keratan sulfate epitope, and total sulfated glycosaminoglycan) were determined in the synovial fluid lavages of dogs with experimental osteoarthritis or disuse atrophy. A model of experimental osteoarthritis was created by transection of the anterior cruciate ligament of the right knee; studies were carried out 6 and 12 weeks after surgery. Joint disuse was studied at 4 and 8 weeks after initiation of the disuse. Recovery after disuse also was studied in joints that had 3 weeks of remobilization after 4 or 8 weeks of disuse. Synovial fluid lavages from the right knee joints of untreated animals were used as controls. The concentrations of keratan sulfate epitope, sulfated glycosaminoglycan, and link protein in the synovial fluid lavages at 6 and 12 weeks after transection of the anterior cruciate were elevated compared with the control values. Similar analysis of the fluid after disuse showed that the levels of keratan sulfate epitope and sulfated glycosaminoglycan were increased compared with the control levels and the levels after transection. However, the concentration of link protein in the fluid after disuse was not significantly different from the control level. The levels of keratan sulfate epitope and sulfated glycosaminoglycan in the synovial fluid lavages after disuse with recovery were high, but the levels of link protein remained low. The results indicate that the catabolism of proteoglycan aggregates in articular cartilage during early osteoarthritis and disuse is different. The determination of keratan sulfate epitope in synovial fluid lavages appears to provide a relatively general indication of proteoglycan catabolism, whereas increased levels of link protein may be more indicative of cartilage degeneration.

Compressive mechanical properties of the human anulus fibrosus and their relationship to biochemical composition.

To enhance understanding of the biomechanical role of the intervertebral disc, the compressive properties and biochemical composition of nondegenerate samples of anulus fibrosus were determined as a function of radial position, region, and level. Because of the large swelling propensity of this tissue, a method was developed to test excised specimens while maintaining their in situ geometry and hydration. Using an analysis based on linear biphasic theory, the compressive modulus, hydraulic permeability, and isometric swelling pressure of the anulus fibrosus were determined and correlated with the tissue composition. The findings indicate that the anulus fibrosus is inhomogeneous, with regional and radial variations in both material properties and biochemical composition. The results of this study suggest that both structural and compositional factors may determine the mechanical behavior.

In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage.

Naproxen is a nonsteroidal anti-inflammatory drug commonly used in the clinical treatment of joint disease. In this study, its effect in vivo on the biochemical composition, metabolic activities, and metalloproteinase activities of normal canine articular cartilage was analyzed. The articular cartilage from the knee joints of dogs who had been given naproxen for 4 weeks to maintain a serum level of 40-50 micrograms/ml was examined. Control animals were given a placebo. Treatment with naproxen was not found to change the composition (water, collagen, and proteoglycan) of the articular cartilage. The culture studies of cartilage explants indicated that proteoglycan synthesis rates were unaffected by the treatment with naproxen but that proteoglycan release from the tissue was suppressed. Analysis of the cartilage for matrix metalloproteinase activities showed reduced activity of neutral matrix metalloproteinase by 80%, of collagenase by 40%, and of gelatinase by 87%, with no change in activity of acid metalloproteinase or of tissue inhibitor for metalloproteinase. These findings indicate that in vivo treatment with naproxen has the capacity to modulate catabolic activities in articular cartilage.

The in vivo effects of naproxen on canine experimental osteoarthritic articular cartilage: composition, metalloproteinase activities and metabolism.

A canine experimental model of osteoarthritis (OA), generated by arthroscopic transection of the anterior cruciate ligament (ACL) of the knee, was used to investigate the in vivo effects of the NSAID naproxen on the course of cartilage degeneration. The drug was given at the time of surgery, or from before surgery, and for 16 weeks after surgery. Analysis of the articular cartilage showed the naproxen was able to significantly suppress the decrease in proteoglycan content and metalloproteinase activities. The results indicate that pharmaceutical agents have the potential to modulate the progression of degenerative joint disease.

Synovial fluid analyses detect and differentiate proteoglycan metabolism in canine experimental models of osteoarthritis and disuse atrophy.

Canine experimental models of osteoarthritis (OA) and disuse atrophy were used to study cartilage metabolism. The synovial fluids from the OA joints showed elevated levels of keratan sulfate (KS) epitope and link protein, indicating increased catabolism. Analysis of fluids from joints with disuse atrophy showed high levels of KS epitope, but no increase in link protein. Quantitation of a novel chondroitin sulfate (3B3) epitope showed it to be present only in the synovial fluids and articular cartilage of the OA joints. The results indicate that these may be important indicators, or markers, of degenerative joint disease.

Antigenic properties of keratan sulfate: influence of antigen structure, monoclonal antibodies, and antibody valency.

The influence of (a) antigen structure, (b) type of monoclonal antibody, and (c) antibody bivalency on the immunochemical detection and quantification of keratan sulfate (KS) from aggrecan has been studied. Apparent KS epitope levels were determined by immunoglobulin G (IgG)-enzyme-linked immunosorbent assay (ELISA) in preparations of human aggrecan and in a defined series of lower molecular weight proteoglycan preparations generated by proteolytic and alkali treatment of aggrecan. Gel filtration chromatography showed KS epitope to be preferentially detected in the higher molecular weight fragments of the preparations. In single KS chains the epitope was detected in the chains of higher M(r). The ability of the proteoglycan to inhibit in the IgG-ELISA decreased with a reduction in proteoglycan fragment size, ranging between 6- and 260-fold, depending on the antibody used. This was considered to be a cooperative binding effect. With most antibodies, the sensitivity of the IgG-ELISA (represented by the steepness of the inhibition slope) was also reduced with smaller inhibitor sizes. The lowest limit of detectability (the amount of KS required to generate 20% inhibition) varied by up to 60-fold depending on the antibody used. The use of monovalent Fab fragments instead of the whole IgG anti-KS antibody in the ELISA showed that the bivalency of the antibody also affected the quantitation of the assay. In the Fab-ELISA the assay was found to have an increased detectability (by 9.5-fold with aggrecan as the inhibitor), and the proteoglycan fragments and aggrecan all generated parallel inhibition curves. Although the Fab-ELISA was somewhat influenced by the structural presentation of the KS, this was not apparent for small fragments and single chains. Thus the effects of cooperative binding and antibody valency could be overcome and quantitative data could be obtained for all samples, using papain-digested samples and the Fab-ELISA. Application of this assay to analysis of body fluids showed the KS-containing fragments in synovial fluid, serum, and urine were of different sizes and could be quantified.

Correlating magnetic resonance imaging with the biochemical content of the normal human intervertebral disc.

Magnetic resonance imaging was used to determine the T2 relaxation times of prepared proteoglycan solutions and of normal human intervertebral disc tissue from the annulus fibrosus (AF) and nucleus pulposus (NP). The collagen, proteoglycan, and water contents of the disc tissue samples were determined by biochemical assays after they were scanned. Correlations among 1/T2, collagen, proteoglycan, and water contents of the tissue samples and among 1/T2, water, and proteoglycan contents of the proteoglycan solutions were calculated. A moderate negative correlation between 1/T2 and water content was noted for the tissue samples, and a very high negative correlation was found between 1/T2 and water content for the proteoglycan solutions. The very high positive correlation between 1/T2 and proteoglycan content of the proteoglycan solutions is probably due to this negative correlation between 1/T2 and water content. There was no significant correlation between 1/T2 and proteoglycan content of the tissues. The moderate positive correlation between 1/T2 and collagen content is probably due to the high negative correlation between collagen content and water content. No significant correlation was found between the collagen and proteoglycan contents of the tissues. Thus it appears that the data confirm previous reports in the literature that the collagen of the disc tissue functions to control its water content.

Increased release of matrix components from articular cartilage in experimental canine osteoarthritis.

The release rates of specific components of the proteoglycan aggregates (G1 domain, the chondroitin sulfate and keratan sulfate containing portion of the protein core, and link protein) of the articular cartilage of mature beagles were studied at early stages of canine experimental osteoarthritis (OA), generated by transection of the anterior cruciate ligament. Analysis of cartilage explants and synovial fluids indicates that at early stages of experimental OA, there is increased release of the proteoglycan aggregates of the articular cartilage. This involves a release from the tissue of the components of the proteoglycan that are specifically involved with aggregation together with the glycosaminoglycans of the proteoglycan. These components were detected at elevated levels in the media of explants of cartilage from the operated joint, and in the synovial fluids of the operated joints.

Early diagnosis of osteoarthrosis of the temporomandibular joint: correlation between arthroscopic diagnosis and keratan sulfate levels in the synovial fluid.

The role of osteoarthrosis (OA) and proteoglycan degradation in the pathogenesis of temporomandibular joint (TMJ) disorders has not been well established. The orthopaedic literature has demonstrated that proteoglycan degradation plays a significant role in the pathology of many joints. The purpose of this investigation was to determine if levels of immunoreactive keratan sulfate (an important component of cartilage proteoglycans) present in synovial fluid aspirates from TMJs correlated with arthroscopically demonstrated OA. Temporomandibular joint arthroscopy was performed on 25 joints in 20 patients and synovial fluid aspirates were obtained just prior to the insertion of arthroscopic cannulas. The results showed that synovial fluid aspirates from joints that arthroscopically demonstrated OA had significantly higher levels of keratan sulfate than synovial fluid aspirates from those joints that showed no evidence of OA (NON-OA). This study gives support to the theory that the pathogenesis of OA of the TMJ is similar to that of chondromalacia of other synovial joints. The combination of TMJ arthroscopy and synovial fluid analysis is an important model that can be used for investigation of the pathogenesis of TMJ disorders.

Immunochemical studies on the synthesis and secretion of link protein and aggregating proteoglycan by chondrocytes.

Chondrocytes from pig laryngeal cartilage were maintained in culture, and the biosynthesis and secretion of link protein and proteoglycan were studied using immunochemical, biochemical and immunolocalisation techniques. In the presence of monensin there was a dose-dependent inhibition of link protein secretion which was very similar to that of aggregating proteoglycan, and suggested that they followed the same intracellular pathway during biosynthesis. In the presence of cycloheximide there was a similar dose-dependent inhibition of the secretion of both link protein and proteoglycan. Kinetics of secretion following inhibition of synthesis by cycloheximide showed that both proteins had similar intracellular pool sizes. Analysis of protein core and glycosaminoglycan biosynthesis showed that the time for synthesis and glycosylation of proteoglycan was 22 minutes, and this was quickly followed (within 6 minutes) by secretion. Intracellular electron microscopic immunolocalisation using protein A-gold showed link protein to be present in the Golgi cisternae and vesicles, and double-labelling experiments showed link protein only to be detected in vesicles that also labelled for proteoglycan protein core. When chondrocytes were maintained in monolayer culture for 10 days the rate of biosynthesis and secretion of proteoglycan increased although that of link protein remained constant. The control of their biosynthesis was thus shown to be independent. Within 4 hours of secretion a high proportion of link protein was incorporated into proteoglycan aggregates.

Development and significance of antibodies to salmon calcitonin in patients with Paget's disease on long-term treatment.

Sixteen consecutive patients in one unit were studied during long-term treatment of Paget's disease of bone with salmon calcitonin. Eleven patients developed detectable antibody titres at some time during treatment. In one patient with a high antibody titre evidence of resistance to treatment emerged two years after the development of antibodies, but no other patient showed evidence of resistance. The clinical and biochemical response could be maintained in the absence of an acute calcium-lowering effect of calcitonin. Although antibodies often develop during treatment with heterologous calcitonin, they are only rarely the cause of clinical resistance.