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Arthritic temporomandibular joint: correlation of macromolecular contrast-enhanced MR imaging parameters and histopathologic findings.

PURPOSE: To assess the utility of macromolecular contrast material-enhanced magnetic resonance (MR) imaging parameters for determining the histopathologic severity of temporomandibular joint (TMJ) arthritis. MATERIALS AND METHODS: Ovalbumin was used to induce arthritis in the TMJs of 10 previously sensitized adult white rabbits. Five rabbits composed the sham-treated control group. Dynamic spin-echo imaging was performed immediately before and for 30 minutes after injection of macromolecular contrast medium. Histologic specimens of TMJ were assessed quantitatively for arthritis. Changes in MR signal intensity were derived from the synovial and subsynovial tissues of the TMJ, and plasma volume (PV) and permeability surface area product (PS) were calculated. These MR parameters and the arthritic scores were compared between sham-treated and antigen-challenged TMJs. The relationships between MR parameters and histopathologic indexes were also determined. RESULTS: Arthritic TMJs showed marked enhancement of the synovial and subsynovial tissues over the imaging period. PS and all histopathologic indexes of arthritis were significantly greater (P < .005) in antigen-challenged than in sham-treated TMJs. PS demonstrated strong positive relationships with all histologic parameters of arthritis, indicating its utility for assessing the severity of joint inflammation. CONCLUSION: Macromolecular contrast-enhanced MR imaging enables quantification of PS and PV in inflamed joints. This technique may provide insights into the pathogenesis of joint inflammation and noninvasive monitoring of disease severity and treatment response in arthritis.

Albumins↗

Regional quantification of cartilage type II collagen and aggrecan messenger RNA in joints with early experimental osteoarthritis.

OBJECTIVE: Accurate assessment of chondrocyte metabolism is a potentially valuable indicator of cartilage health in osteoarthritis (OA). This study was conducted to explore the anabolic metabolism of chondrocytes early in the natural history of an experimental canine model of OA. METHODS: Competitive reverse transcription-polymerase chain reaction was used to calculate the copy number of type II collagen and the messenger RNA (mRNA) levels of aggrecan core protein in articular cartilage samples obtained from different regions of the femorotibial joint 12 and 39 weeks after cruciate transection. RESULTS: Gene expression of both type II collagen and aggrecan in cartilage samples obtained from experimental joints at both intervals after surgery was elevated significantly compared with that in samples from contralateral control joints. The number of mRNA copies per microgram of DNA of aggrecan exceeded that of type II collagen in control cartilage, but the copy number of type II collagen mRNA exceeded that of aggrecan in OA cartilage. Thus, the ratio of type II collagen-to-aggrecan mRNA copy number (normalized to DNA) was shown to be characteristically altered in cartilage with experimental OA. CONCLUSION: Accurate assessment of multiple gene products in small samples of cartilage taken from focal areas of a joint can be used diagnostically for monitoring chondrocyte metabolism and possibly for staging at least the early phases of this joint disease.

Aggrecans↗

Quantification of anatomic, geometric, and load transfer characteristics of the wrist joint.

The work reported here is an assimilation of 8 years of research, the purpose of which was to gain a better understanding of the normal and abnormal workings of the wrist joint. The results are summarized in three major areas of concentration: descriptive anatomic studies, which include direct measurements of cadaver specimens, biomechanical loading studies to define load distribution through normal and abnormal wrists, and three-dimensional (3D) anatomy studies using solid models derived from computed tomographic (CT) images of in vivo and cadaver wrists. The descriptive anatomic studies used 393 cadaver wrists to evaluate the incidence and distribution of anatomic features, arthroses, chondromalacia, and soft-tissue lesions. The data were analyzed for any statistically significant associations among different variables. The biomechanical studies characterized the biomechanics of the human wrist in a variety of normal, simulated traumatic, and surgically treated conditions. The results of the load studies have provided clinically relevant information on the normal anatomy and functional mechanics of the wrist as well as guidelines for the treatment of a number of different fractures and ligament injuries. The 3D anatomic studies use quantitative analysis of 3D reconstructions of CT scan data to build a normative database of carpal bone morphology. Thirty-five wrists were imaged in a CT scanner. Quantitative measurements of volume, surface area, maximum length, and intercarpal distances were than assessed. A reliable 3D carpal height ratio (3DCHR) was calculated by dividing the capitate maximum length by the carpal height, which is the minimum distance between the fourth metacarpal and the radius.

Adolescent↗

Bone and joint neuropathy in rats with type-2 diabetes.

We have previously demonstrated that Goto-Kakizaki (GK) rats with spontaneous type-2 diabetes and peripheral neuropathy exhibit regional osteopathic changes. In the present study on 18 GK rats and 21 control Wistar rats, the occurrence of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the autonomic neuropeptide Y (NPY) was analysed in bone and joints, dorsal root ganglia and lumbar spinal cord by immunohistochemistry and radioimmunoassay (RIA). Immunohistochemistry disclosed a predominance of immunoreactivities in vessel-related nerve fibers, although some were also seen in free terminals. While SP, CGRP and NPY in periosteum, cortical bone and synovium was confined to neuronal tissue, the bone marrow in addition exhibited an abundance of NPY-positive megakaryocytes. Apart from this cellular source of NPY, the observations suggest that the three neuropeptides analysed in bone and joints are of neuronal origin. Quantification by RIA showed a significant decrease of NPY in cortical bone (-36%), bone marrow (-66%) and ankle (-29%) of GK rats. CGRP was decreased in the spinal cord (-19%) and dorsal root ganglia (-26%) but was unchanged in bone and joints, as with SP. Given the suggested anabolic role of NPY and CGRP on bone, neuropeptidergic deficit in diabetes may prove to be an important factor underlying the development of regional osteopenia.

Animals↗

[Radiological staging index of osteoarthrosis].

The association of joint pain with radiological changes (such as osteophytes, joint space narrowing, and sometimes, bone cysts and erosion) is the most commonly criteria used in daily medical practice for the diagnosis of osteoarthrosis. However, these findings do not allow objective quantification of the intensity of the joint involvement. In an attempt to measure quantitatively the radiological lesions encountered in osteoarthrosis the authors elaborated a radiological index based on the following parameters: I. severity of radiological changes, II. area of the affected joint and III. number of affected joints. The application of this index in the medical practice allows a simple way of quantification of radiological lesions of osteoarthrosis and thus, a better clinical monitorization of the disease.

Arm↗

Cartilage oligomeric matrix protein and hyaluronan levels in synovial fluid from horses with osteoarthritis of the tarsometatarsal joint compared to a control population.

REASONS FOR PERFORMING STUDY: Quantification of cartilage oligomeric matrix protein (COMP) levels within synovial fluid from the tarsometatarsal joint has not previously been reported and an effective synovial fluid marker would allow monitoring of disease progression and treatment. OBJECTIVES: To quantify levels of COMP and hyaluronan (HA) in synovial fluid from the tarsometatarsal joint, identify differences in levels from horses with osteoarthritis (OA) of the tarsometatarsal joint compared to a control population and to correlate levels with radiographic changes in horses with OA. METHODS: Synovial fluid was collected from the tarsometatarsal joint of 25 horses without hindlimb lameness (controls) and 25 lame horses, subjected to analgesia of the joint. COMP concentrations were measured using a homologous inhibition ELISA. Immunoblots of synovial fluid from 3 lame horses and 3 controls were performed to identify fragmentation of COMP. Hyaluronan (HA) concentration in synovial fluid was determined using a competition ELISA. Radiographs of the lame horses with OA were scored and correlated with levels of COMP and HA. RESULTS: Concentrations of COMP in OA of the tarsometatarsal joint were significantly lower than in the control samples. An additional fragment band of COMP (approximately 30 kDa) was identified on the immunoblots of the horses with OA and this fragment was not identified in controls. No significant difference was identified in the HA or HA:COMP ratio between lame and control horses. There was no correlation between levels of synovial fluid COMP and HA, and radiographic changes. CONCLUSIONS AND POTENTIAL RELEVANCE: Lowered levels of COMP in synovial fluid of tarsometatarsal joints correlates with the presence of osteoarthritis. However, a single value cannot be used to stage the disease process. Levels of HA may not be a useful marker for this disease. Decreased, rather than increased COMP levels, may reflect significant loss of cartilage in established osteoarthritis. A specific assay for the COMP fragment generated with osteoarthritis may allow the earlier detection of clinical cases.

Animals↗

Quantification of hemostatic proteins and activation products in synovial fluids from arthritic joints prior to and after induction of chemical synoviorthesis.

Synovial fluids drawn from joints of patients suffering from rheumatoid arthritis were investigated for their concentrations of proteins and activation markers of the complement, coagulation and fibrinolytic systems. A broad spectrum of plasmatic inhibitors and other hemostatic proteins were detectable by immunologic assays. Compared to normal plasma concentration ranges, levels of alpha 2-antiplasmin, antithrombin III, heparin-cofactor II, factor H, alpha 2-macroglobulin, inter-alpha-trypsin inhibitor, fibrinogen and particularly high molecular weight kininogen were found to be decreased when corrected for total protein content. However, highly elevated levels of C-reactive protein, factor XIII, PMN-elastase, prothrombin fragment F1+2, thrombin-antithrombin III, plasmin-antiplasmin and terminal complement-complexes as well as C5a were determined. Eight and 24 hours after induction of chemical synoviorthesis, a general increase in most of the parameters was observed. Statistically significant alterations were found for C1-inhibitor, factor H, alpha 1-antitrypsin, inter-alpha-trypsin inhibitor, factor XIII, protein C, thrombin-antithrombin III complexes and C5a.

Arthritis, Rheumatoid↗

Thermography in the assessment of peripheral joint inflammation--a re-evaluation.

The reproducibility and sensitivity of quantitative infra-red thermography as a measure of peripheral joint inflammation was reassessed. Experiments were carried out in a temperature-controlled room at 20 degrees C. Initial stabilization experiments showed that in normal, medium sized, joints, there was an initial rapid cooling phase followed by a slower cooling phase which lasted longer than two hours. In the knees the differences between normal and active rheumatoid joints increased the longer patients remained in the room but for practical reasons a 30-minute stabilization period was subsequently chosen. In views of hands and fingers, rebound increases in skin temperature after entering the room, together with lesser differences between inflamed and non-inflamed joints, were found. The results suggested that the thermographic technique examined was adequate for detecting inflammatory changes in knee, ankles and elbows but unsatisfactory for quantification of inflammation in the small joints of the hands.

Adult↗

No loss of cartilage volume over three years in patients with knee osteoarthritis as assessed by magnetic resonance imaging.

OBJECTIVE: Magnetic resonance imaging (MRI) has the potential to provide accurate quantification of structural changes in joint disease, with sensitivity to change, as it can provide direct visualization of the cartilage and bone. In this study, we investigated whether knee cartilage volume, as assessed by MRI, is sensitive to change over time in patients with osteoarthritis (OA). DESIGN: Sixteen patient volunteers (10 male, six female) with established OA of the knee were entered into the study and demographic data recorded. At baseline, 12 months and 37+/-2 months, patients underwent simple measures of disease severity, as well as extended weight-bearing AP knee X-rays. In addition the patient's index knee was imaged using MR at 1.0 T using a 3-D spoiled gradient-echo sequence with fat-suppression, repetition time 50 ms, echo time 11 ms, flip-angle 40 degrees, sagittal slice thickness 1.56 mm and in-plane pixel resolution 0.55 mm. Manual image segmentation was performed on all knee cartilage compartments and the respective cartilage volumes determined. RESULTS: Eleven of the original patients recruited completed the 3-year study. Radiographic features indicated that the majority had a spectrum of well-established OA at entry. The average decrease in medial tibiofemoral joint space width was 0.21+/-0.37 mm (mean+/-S.D.). Comparison of MR images at baseline and 37+/-2 months indicated little evidence of cartilage lesion shape or size change in any of the compartments. There was no significant MRI volume change in any of the knee cartilage compartments over the course of 1 year. The change in total knee cartilage volume, as measured by MRI, was a loss of only 1.6%, or 0.36+/-1.3 ml (mean+/-S.D.), over the 3 years. CONCLUSIONS: The failure to identify loss of cartilage volume over 3 years in this cohort of patients with established knee OA using MRI challenges the face validity of this endpoint to assess structural changes in OA.

Aged↗

Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee.

BACKGROUND: Optical imaging is an attractive non-invasive way to evaluate the expression of a transferred DNA, mainly thanks to its lower cost and ease of realization. In this study optical imaging was evaluated for monitoring and quantification of the mouse knee joint and tibial cranial muscle electrotransfer of a luciferase encoding plasmid. Optical imaging was applied to study the kinetics of luciferase expression in both tissues. RESULTS: The substrate of luciferase (luciferin) was injected either intraperitonealy (i.p.) or in situ into the muscle or the knee joint. Luminescence resulting from the luciferase-luciferin reaction was measured in vivo with a cooled CCD camera and/or in vitro on tissue lysate. Maximal luminescence of the knee joint and muscle after i.p. (2.5 mg) or local injection of luciferin (50 microg in the knee joint, 100 microg in the muscle) were highly correlated. With the local injection procedure adopted, in vivo and in vitro luminescences measured on the same muscles significantly correlated. Luminescence measurements were reproducible and the signal level was proportional to the amount of plasmid injected. In vivo luciferase activity in the electrotransfered knee joint was detected for two weeks. Intramuscular electrotransfer of 0.3 or 3 microg of plasmid led to stable luciferase expression for 62 days, whereas injecting 30 microg of plasmid resulted in a drop of luminescence three weeks after electrotransfer. These decreases were partially associated with the development of an immune response. CONCLUSION: A particular advantage of the i.p. injection of substrate is a widespread distribution at luciferase production sites. We have also highlighted advantages of local injection as a more sensitive detection method with reduced substrate consumption. Besides, this route of injection is relatively free of uncontrolled parameters, such as diffusion to the target organ, crossing of biological barriers and evidencing variations in local enzymatic kinetics, probably related to the reaction medium in the targeted organ. Optical imaging was shown to be a sensitive and relevant technique to quantify variations of luciferase activity in vivo. Further evaluation of the effective amount of luciferase in a given tissue by in vivo optical imaging relies on conditions of the enzymatic reaction and light absorption and presently requires in vitro calibration for each targeted organ.

Animals↗

Synovial volume--a marker of disease severity in rheumatoid arthritis? Quantification by MRI.

Volumes of synovial membrane and joint effusion were determined by magnetic resonance imaging (MRI) in patients with inflammatory gonarthritis. Volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted MR-images. Ten knees with clinically active gonarthritis (CAG), 8 knees with clinically inactive gonarthritis (CIG) and 5 healthy controls (HC) were examined. The synovial volume of CAG-, CIG- and HC-knees were significantly different. The median volumes were 79 ml, 21 ml and 3 ml, respectively. Synovial and effusion volumes were highly correlated. A selected sagittal one-slice volume showed a high correlation to the total volumes. The reliable quantification of synovial and effusion volumes could be useful in the assessment of disease severity and as an outcome measure to treatment.

Arthritis, Rheumatoid↗

[Radiation synovectomy of the knee joint: Evaluation of bremsstrahlung-detection by using a corpse phantom].

AIM: Multiple procedures for the quantification of activity leakage in radiation synovectomy of the knee joint have been described in the literature. We compared these procedures considering the real conditions of dispersion and absorption using a corpse phantom. METHODS: We simulated different distributions of the activity in the knee joint and a different extra-articular spread into the inguinal lymph nodes. The activity was measured with a gamma-camera. Activity leakage was calculated by measuring the retention in the knee joint only using an anterior view, using the geometric mean of anterior and posterior views, or using the sum of anterior and posterior views. The same procedures were used to quantify the activity leakage by measuring the activity spread into the inguinal lymph nodes. In addition, the influence of scattered rays was evaluated. RESULTS: For several procedures we found an excellent association with the real activity leakage, shown by an r(2) between 0.97 and 0.98. When the real value of the leakage is needed, e. g. in dosimetric studies, simultaneously measuring of knee activity and activity in the inguinal lymph nodes in anterior and posterior views and calculation of the geometric mean with exclusion of the scatter rays was found to be the procedure of choice. CONCLUSION: When measuring of activity leakage is used for dosimetric calculations, the above-described procedure should be used. When the real value of the leakage is not necessary, e. g. for comparing different therapeutic modalities, several of the procedures can be considered as being equivalent.

Humans↗

Quantification and age-related distribution of articular cartilage degeneration in the equine fetlock joint.

REASONS FOR PERFORMING STUDY: The equine fetlock joint has the largest number of traumatic and degenerative lesions of all joints of the appendicular skeleton. OBJECTIVE: To gain insight into the distribution of cartilage degeneration across the articular surface in relation to age in order better to understand the dynamic nature and progression of osteoarthritis (OA). HYPOTHESIS: That there would be a specific age-related distribution pattern of cartilage degeneration in the equine metacarpophalangeal joint. METHODS: The proximal articular cartilage surfaces of the first phalanges (P1) of 73 slaughter horses (age range 0.4-23 years) with different stages of osteoarthritis were scored semiquantitatively on a 0 to 5 scale and also assessed quantitatively using the cartilage degeneration index (CDI(P1)), which ranges from 0 to 100%. Furthermore, CDI values were determined for special areas of interest; medial dorsal surface (CDI(mds)), lateral dorsal surface (CDI(lds)), medial central fovea (CDI(mcf)) and lateral central fovea (CDI(lcf)). Correlations were calculated for CDI(P1) values and CDI values at the specific areas of interest with macroscopic scores and with age. RESULTS: There was a high correlation between the semiquantitative macroscopic score and the quantitative CDI(P1) values (r = 0.92; P < 0.001). A macroscopic score of 0 (i.e. no obvious cartilage degeneration) corresponded with a CDI(P1) mean +/- s.e. value of 25 +/- 2.8% and a macroscopic score of 5 (i.e. severe cartilage degeneration in localised areas) with a mean +/- s.e. value of 38.1 +/- 7.9%. There was a moderate but highly significant correlation between the CDI(P1) value and the age of the horses (r = 0.41; P < 0.001). Highest CDI values were calculated for the medial dorsal surface (from 10.6 +/- 2.8% at macroscopic Grade 0 to 63.1 +/- 8.4% at Grade 5). At the lateral dorsal surface, these values were 5.9 +/- 1.4% and 47.2 +/- 10.4%, respectively. The CDI(mcf) and CDI(lcf) were significantly lower (P < 0.05) than the CDI(mds) and CDI(lds) at all grades. The CDI(mcf) ranged from 1.0 +/- 2.9% at Grade 0 to 43.7 +/- 9.1% at Grade 5; laterally, these values were 1.5 +/- 2.6% and 15.2 +/- 6.2%, respectively. CONCLUSIONS: CDI grading increased from lateral to medial and from central to dorsal. This specific distribution pattern confirms the heterogeneous nature of the OA process and strongly supports an important role for biomechanical loading, superimposed on age-related changes, in the spread of the disorder over the joint. POTENTIAL RELEVANCE: Knowledge of the development of OA across the articular surface is essential for understanding the dynamic nature and progression of the disease and can form a basis for improvements in diagnostic and therapeutic approaches to degenerative joint disease.

Age Distribution↗

A static dynamometer measuring simultaneous torques exerted at the upper limb.

The majority of available dynamometers are designed to measure force or torque in one specific direction, one joint at a time. For the quantification of motor incoordination in neurological patient populations, these dynamometers provide limited information about the global behavior of the limb under investigation. This report describes the potential use and function of a static dynamometer measuring torques exerted simultaneously at the shoulder (flexion-extension, abduction-adduction, internal-external rotation), elbow (flexion-extension), and forearm (pronation-supination). Orthogonal forces were measured at the arm and wrist using strain gauge transducers interfaced with a laboratory computer. The lever arms were specified to a software program and the joint torques were calculated in real time according to static equilibrium equations. The use of the dynamometer is illustrated by characterizing for one hemiparetic subject, the joints torques recorded at the shoulder, elbow, and forearm during isolated submaximal grip exertions at different force levels on both sides. The torques generated at the shoulder, elbow and forearm during the hand grip tasks on the affected side were significantly higher than those obtained on the nonaffected side and increased with the grip force level. These differences probably reflect the loss of movement selectivity observed following a lesion in the central nervous system. Further studies are currently being undertaken in neurological patient populations to characterize and quantify motor deficits using this dynamometer. As a long term goal, we hope that the method and technologies described here will contribute to the evaluation and rehabilitation of these populations.

Biofeedback, Psychology↗

Quantification of responses from proprioceptive neurons in the limbs of the crab, Cancer magister.

In the limbs of crustaceans, proprioception is monitored by chordotonal organs. One in particular, MC1, is arranged in a manner that is accessible for single unit recording of primary sensory neurons while simulating joint movement. The movement-sensitive cells are of two types, those sensitive to relaxation or to elongation of the chordotonal strand which corresponds to flexion or extension of the meropodite-carpopodite joint, respectively. A statistical method for the quantification of these movement-sensitive proprioceptive neuronal responses was implemented. This statistical index, eta(2), should allow neuronal responses recorded in different laboratories to be easily and quantitatively compared. In addition, an eta(2) value can be assigned to individual cells which represents a cell's consistency and degree to which the response is related to the stimulus. We found some cells to have a high eta(2) and to be consistent in their activity while other cells had a high degree of variability with low eta(2) values. J. Exp. Zool. 284:629-636, 1999.

Action Potentials↗

Synovial adhesions are more important than pannus proliferation in the pathogenesis of knee joint contracture after immobilization: an experimental investigation in the rat.

OBJECTIVE: To measure intraarticular pannus proliferation after early and prolonged joint immobility using an animal model. METHODS: Forty rats underwent unilateral immobilization of a knee joint with an internal fixator for periods of 2, 4, 8, 16, and 32 weeks. Twenty rats received sham surgery. The knee joints were harvested and processed for histological examination. The synovial intima length and the subintimal area were measured on standardized sagittal sections with image analysis software. The measurements were recorded with regard to their location (anterior or posterior; superior or inferior). RESULTS: Intra and interrater reliabilities for all measurements were > 87.9%. The synovial intima length was smaller in immobilized knees than in controls at all time points. At 4 and 32 weeks, the difference was statistically significant (p < 0.05). The differences were marked in the posterior synovium, where the intima length of immobilized knees was significantly smaller than in controls after 4, 8, 16, and 32 weeks of immobilization (p < 0.05). The subintimal area was comparable in immobilized and control knees at all time points. CONCLUSION: We standardized the quantification of intraarticular pannus in a joint contracture model after immobility of up to 32 weeks' duration. This study revealed a significant decrease in synovial intima length but no change in the subintimal area of immobilized knees compared with controls. The decrease in synovial intima length with immobility suggests that adhesions of synovium villi rather than pannus proliferation are the major pathophysiological changes leading to contracture after immobility.

Animals↗

Precise 3D skeletal kinematics using fast phase contrast magnetic resonance imaging.

PURPOSE: To examine the precision of cine-phase contrast (PC) magnetic resonance imaging (MRI) techniques as applied to the quantification of three-dimensional knee joint kinematics. MATERIALS AND METHODS: The knee joints of eight healthy volunteers were studied using three different dynamic, PC MRI protocols: cine-PC (one average), cine-PC (two averages), and cine-PC with segmented phase encoding (fast-PC). RESULTS: Fast-PC has comparable precision, shorter scan times, and improved subject interexam variability (SIEV) compared to cine-PC (two averages). Further, cine-PC (one average) has low precision and high SIEV, making fast-PC the preferred method of data acquisition. Specifically, the precision of fast-PC MRI in measuring knee joint kinematics ranged from 0.22 degrees -1.16 degrees. CONCLUSION: A cine-PC MRI technique utilizing segmented phase encoding (fast-PC MRI) acquires dynamic data at a faster rate than other PC imaging protocols, without compromising data precision. Being able to acquire precise 3D kinematics with shorter imaging times is critical if we are to use this technique to advance ongoing research in musculoskeletal kinematics.

Adult↗

In vivo quantification of proteoglycan synthesis in articular cartilage of different topographical areas in the murine knee joint.

We developed a method of quantitative measurement of the synthesis of proteoglycans in different areas of the patella and the tibial plateau of the mouse. After incorporation of radioactive sulfate in vivo, the patella was divided with a punch into a central and a peripheral part. A central medial and a central lateral part were taken from the tibial plateau to measure the synthesis of proteoglycans. The synthesis was determined in normal joints and at different intervals after intra-articular injection of sodium iodoacetate and was compared with autoradiographs of whole joint sections. Although considerable variation in sulfate incorporation was found within a group on particular days after induction of osteoarthritis, the variation among experiments was low. Comparison with autoradiographs showed that this new method makes it possible to quantify proteoglycan synthesis by incorporation of radioactive sulfate in different topographical areas of the murine knee joint.

Animals↗