Rabbit Model of Extending Knee Joint Contracture: Progression of Joint Motion Restriction and Subsequent Joint Capsule Changes after Immobilization.

This study aimed to develop a rabbit model of knee contracture in extension and investigate the natural history of motion loss and time-dependent changes in the joint capsule after immobilization. We immobilized the unilateral knee joints of 32 rabbits by maintaining the knee joint in a plaster cast at full extension. Eight rabbits were euthanized at 2, 4, 6, and 8 weeks after casting, respectively, and the lower extremities were disarticulated at the hip joint. Eight control group rabbits that did not undergo immobilization were also examined. We assessed the progression of joint contracture by measuring the joint range of motion, evaluating the histologic alteration of the capsule, and assessing the mRNA levels of transforming growth factor ß1 (TGF-ß1) in the anterior and posterior joint capsules. After 2 weeks of joint immobilization, the knee joint range of motion was limited, the synovial membrane of the suprapatellar and posterior joint capsules was thickened, the collagen deposition was increased, and the mRNA levels of TGF-ß1 were elevated in the anterior and posterior joint capsules. These changes progressed rapidly until 6 weeks of immobilization and may advance slowly after 6 weeks. Joint contracture developed at the early stage of immobilization and progressed over time. The changes in the anterior and posterior joint capsules after joint immobilization may contribute to the limitation in flexion. The elevated mRNA expression of TGF-ß1 may be related to joint capsule fibrosis and may be one of the causes of joint contracture.

Poly(ethylene glycol)/chitosan/sodium glycerophosphate gel replaced the joint capsule with slow-release lubricant after joint surgery.

Body fluid is normally the only lubricant after joint replacement surgery, but wear problems have occurred because body fluid has poor lubrication ability. However, traditional lubricant would be diluted by body fluids and then absorbed by the human body. Therefore, an injectable gel with the ability to slow-release lubricant was designed to replace the joint capsule. The proposed gel, poly(ethylene glycol)/chitosan/sodium glycerophosphate (PEG/CS/GP) composite gel was then tested. The tribology results showed that the PEG/CS/GP gel had excellent slow-release properties, especially under pressure, and the PEG played an important role in improving the gel's rheological and mechanical properties. Moreover, this study revealed that the release solution had a good lubrication effect because the PEG and GP could crosslink via the hydrogen bond effect.

More histologic and ultrastructural degenerative signs in the subscapularis tendon and the joint capsule in male patients with shoulder impingement.

PURPOSE: The purpose of the present study was to analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with shoulder impingement syndrome (SAIS) and compare them with samples from male patients with post-traumatic recurrent shoulder instability. The hypothesis of the study was that patients with SAIS would have more histologic and ultrastructural degenerative changes in their subscapularis tendon and joint capsule than patients with post-traumatic recurrent shoulder instability. METHODS: Male patients scheduled for surgery, with either subacromial decompression or Bankart reconstruction, were included. Four biopsies from each patient were obtained from the capsule and four from the subscapularis tendon during arthroscopic surgery. The histologic characteristics and the presence of glycosaminoglycans were assessed using the light microscope, and the ultrastructure was assessed using a transmission electron microscope. RESULTS: Eight patients, median age 53 (45-74) years (p < 0.0001), were included in the impingement group, and 12 patients, median age 27 (22-48) years, were included in the instability group. The histologic assessment revealed significantly higher cellularity and total degeneration score in the capsule (p = 0.016 and p = 0.014 respectively) in patients with subacromial impingement compared with the instability patients. The corresponding finding was not made for the subscapularis tendon. The ultrastructural evaluation revealed that the instability patients had more fibrils with a large diameter (indicating less degeneration) in both the subscapularis tendon and the capsule compared with the impingement patients (p < 0.0001). CONCLUSION: Male patients with subacromial impingement have more histologic and ultrastructural degenerative changes in their shoulder compared with patients with post-traumatic recurrent shoulder instability. CLINICAL RELEVANCE: It appears that in patients with subacromial impingement, the whole shoulder joint is affected and not only the subacromial space. It is the opinion of the authors that intra-articular therapeutic injections could be tried more often in these patients. LEVEL OF EVIDENCE: III.

Clinical, instrumental, serological and histological findings suggest that hemophilia B may be less severe than hemophilia A.

Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (<10, 10-50, >50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10-50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (P<0.001 and P=0.03, respectively), while that with less than 10 hemarthrosis was higher in hemophilia B (P<0.0001). World Federation of Hemophilia (36.6 vs. 20.2; P<0.0001) and ultrasound (10.9 vs. 4.3; P<0.0001) score mean values were significantly higher in hemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (P<0.0001 and P=0.006, respectively). Osteoprotegerin expression was markedly reduced in synovial tissue from hemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A.

MALDI imaging of predictive ferritin, fibrinogen and proteases in haemophilic arthropathy.

Arthropathy as a result of repeated joint bleeding is a severe complication in patients with haemophilia. In the evaluation of synovial tissue specimens, histology alone is non-specific and there is considerable morphological overlap with other joint diseases. Formalin-fixed paraffin-embedded specimens are available in pathological institutes and can be studied to understand the pathogenesis of haemophilic arthropathy. A powerful technique to identify hundreds of proteins in a tissue section combining proteomics with morphology is imaging mass spectrometry (IMS). We determined whether matrix-assisted laser desorption/ionization (MALDI) IMS can be used to identify and map protein signatures in the synovial tissue of patients with haemophilic arthropathy. MALDI IMS was applied to synovial tissue of six patients with haemophilic arthropathy. We detected several peaks predictive in mass with ferritin light (m/z 1608) and heavy chain (m/z 1345), alpha- (m/z 1071) and beta (m/z 1274) haemoglobin subunits, truncated coagulation factor VIII peptide (m/z 1502, 1176), beta- and gamma fibrinogen peptides (m/z 980, 1032, 1117 and 1683), and annexin A2 (m/z 1111, 1268, 1460, 2164). In addition, the distribution of these proteins in synovial tissue sections was demonstrated. MALDI IMS identified and mapped specific proteins in the synovial membrane of patients with haemophilic arthropathy known to be involved in the pathogenesis of other joint diseases. This technique is a powerful tool to analyse the distribution of proteins in synovial tissue sections.

Synovial deposition of wild-type transthyretin-derived amyloid in knee joint osteoarthritis patients.

OBJECTIVE: To investigate histological features of deposited amyloid in the synovial tissue and its clinical significance in knee joint osteoarthritis (OA) patients. METHODS: We prospectively enrolled 232 consecutive patients who underwent arthroplasty or total replacement of the knee joint for treatment of OA. Congo red staining and immunohistochemistry were performed in the synovial tissue obtained at surgery. When transthyretin (TTR)-derived amyloid was positive, we analyzed all 4 exons of the TTR gene using the direct DNA sequencing method in order to detect mutations. RESULTS: We analyzed 322 specimens in this study. Twenty-six specimens (8.1%) obtained from 21 patients (5 men and 16 women; mean, 79.0 ± 4.6 years) showed deposition of amyloid, which was positively stained with the anti-TTR antibody. Eighteen patients showed inhomogeneous accumulations of amyloid in the loose connective tissue under the synovial epithelia sometimes with nodule formation, while in the remaining three, small vessels in the adipose tissue were involved. Medical records of these patients revealed nothing remarkable in the clinical course, laboratory data or macroscopic intraarticular findings at surgery. No mutations were detectable in the TTR gene analysis. CONCLUSION: Wild-type TTR-derived amyloid may affect the synovial tissue as a result of long-term mechanical stress or as a part of senile systemic amyloidosis in approximately 8% of knee joint OA patients. No obvious clinical significance was found in synovial deposition of amyloid.

Ceramic debris in hip prosthesis: correlation between synovial fluid and joint capsule.

Detection of ceramic particles in synovial fluids allows early diagnosis of ceramic damage, but there is no evidence of a relationship between ceramic debris in the articular space and in the joint capsule. The aim of the present study is to verify if the particles isolated in the synovial fluid are comparable with those stored in the capsular tissue. Twenty-one patients were enrolled. Both synovial fluid and capsular samples were collected during revision surgery and ceramic particles were isolated and analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis. It resulted a significant correlation between the samples couples (18 out of 21). This study confirms that the synovial fluid analysis can give a clear definition of the presence of particles in the joint capsule.

Lead and calcium content in the human hip joint.

Concentration of lead in bone, unlike in soft tissues, increases during the lifetime and reflects severity of exposure to this element. The main aim of the study was to determine concentrations of lead and calcium and to find possible relationship between calcium and lead in the tissues of the hip joints obtained from inhabitants of the Upper Silesian Industrial Area. We also attempted to identify factors that might affect this relationship. The samples were harvested intraoperatively during total hip replacement procedures; in most cases, the indication for the surgery was hip osteoarthritis. Concentrations of lead and calcium were measured with a Pye Unicam SP-9 acetylene-oxygen flame atomic absorption spectrometer. The highest mean concentration of lead was found in the cancellous bone from the femoral head, followed by articular cartilage, cortical bone and the intertrochanteric cancellous bone (0.75 µg/g). The smallest concentration was found in the joint capsule (0.19 µg/g). The highest mean concentration of calcium was found in cancellous bone from the femoral head, followed by cancellous bone from the intertrochanteric area, cortical bone, articular cartilage and joint capsule. The concentration of lead showed no correlation with sex. The bone concentration of calcium decreased with age. In the analysed hips, this finding was true in the cortical bone, as well as in the cancellous bone of the intertrochanteric area. Statistically significant correlation between calcium and lead was found only in the hip articular cartilage.

[Distribution and expression of TGF-ß2 in the capsule of children with developmental dysplasia of the hip].

OBJECTIVE: This study examined the distribution and expression of transforming growth factor-ß2 (TGF-ß2) in the hip capsule of children with developmental dysplasia (dislocation) of the hip (DDH) and non-DDH children in order to investigate the roles of TGF-ß2 in hip joint laxity. METHODS: Eight children with DDH and eight age- and gender-matched non-DDH children (control group) were enrolled. The immunohistochemical technique (S-P method) was used to examine the distribution and content of TGF-ß2 in the hip capsule. Semiquantitative RT-PCR method was used to detect mRNA expression of TGF-ß2 in the hip capsule. The quantitative analysis of TGF-ß2 was performed by professional image software. RESULTS: A high expression of TGF-ß2 was observed in the synovial layer with fibroblast regularly arranged parallel to the joint surface. There was decreased expression of TGF-ß2 in the fibrous layer of the capsule. The percentage of positive fibroblasts and the gray-scale density in the fibrous layer in the DDH group were significantly lower than those in the control group (P < 0.01). TGF-ß2 mRNA expression in the DDH group decreased compared with that in the control group (P < 0.05). CONCLUSIONS: The decreased TGF-ß2 in distribution, content and mRNA expression in the hip capsule might contribute to hip joint laxity in children with DDH.

Development of a shoulder contracture model in rats.

HYPOTHESIS: The capsular tissue is responsible for the pathogenesis of the shoulder contracture. MATERIALS AND METHODS: The glenohumeral joint of Sprague-Dawley rats was immobilized using internal fixation (immobilized group). The control group underwent a sham operation (sham group). To assess the range of motion, the glenohumeral joint angle was measured repeatedly under same torque in 6 conditions: after removal from the trunk, after removal of the outer muscles other than rotator cuff after removal of the rotator cuff muscles, and after 3 types of partial capsulotomy. The abduction angle and total rotation angles were measured. The length of the synovial intima was measured with hematoxylin-eosin-stained specimens. Immunohistochemical study for type III collagen was also performed. RESULTS: No significant differences were found in the range of motion until all the muscles were removed. The abduction angle increased significantly after serial capsulotomy in the immobilized group. Even after the capsulotomy, however, this angle remained significantly less than that in the sham group. There was a similar trend for the total rotation angle. There was morphological change in the synovium of the immobilized group; the significant decrease of synovial length and strong staining of type III collagen. DISCUSSION: Our results show that capsule might play important role for contracture formation. Decrease of the synovial length might reflect synovial adhesion. Strong expression in Type III collagen might be related to joint stiffness. CONCLUSION: A contracture model was successfully established. Changes in the capsule and synovium might play an important role in occurrence of contracture.

Myofibroblast upregulators are elevated in joint capsules in posttraumatic contractures.

We hypothesized specific growth factors are increased in the elbow capsules of patients with post traumatic elbow contractures. A model of surgically induced joint contracture in rabbit knees was developed to study the growth factor expression in joint contractures. This study demonstrates this model mimics the human condition and analyzes how the growth factor levels decrease with time in rabbit knees with contractures. Reverse transcription polymerase chain reaction was used to measure mRNA levels of transforming growth factor-beta1, connective tissue growth factor, ED-A of fibronectin, and alpha-smooth muscle actin normalized to a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. In the joint capsules of patients with elbow contractures, mRNA levels were increased for transforming growth factor- beta1, connective tissue growth factor, and alpha-smooth muscle actin. In the joint capsules of rabbit knees with contractures, mRNA levels were increased for transforming growth factor- beta1, connective tissue growth factor, ED-A of fibronectin, and alpha-smooth muscle actin. The mRNA levels for transforming growth factor-beta1, connective tissue growth factor, and alpha-smooth muscle actin decreased with time in rabbit knees. The elevated levels of these myofibroblast up-regulators and fibrogenic growth factors could explain the previously reported increase in myofibroblasts and collagen mRNA levels. The rabbit knee model correlated well with the human post traumatic elbow contractures.

[Changes in the articular compartment in advanced osteoarthritis]. / Zmeny v kloubním kompartmentu u pokrocilé osteoartrózy.

PURPOSE OF THE STUDY: Both synovial and bone forms of osteoarthritis (OA) are characterized by inflammatory processes in the articular compartment. Increasing evidence suggests that changes in bone tissue are important for the deterioration or loss of joint function. Therefore it is reasonable to shift emphasis from research on cartilage to that on other articular tissues, particularly on subchondral bone. The aim of the study was to demonstrate the involvement of several cytokines in OA development and, on the basis of changes of joint markers, to assess the extent of inflammatory process. MATERIAL: A total of 60 patients with an osseous form of osteoarthritis of the knee joint (28 patients) or the hip joining (32 patients) underwent total knee or hip arthroplasty. The mean age of our patients was 66.7 +/- 10.4 years. Preoperative clinical and radiographic examinations were carried out as well as routine laboratory tests on blood and urine. Samples of urine, blood serum (BS) and synovial fluid (SF), extracts from cartilage (CA) and synovial membrane (SM) and granulation bone tissue were analysed for markers indicating the presence of inflammatory processes in joints. METHOD: The following markers of inflammatory activity in the bone compartment were investigated: pyridinoline (PYR), deoxypyridinoline (D-PYR), bone alkaline phosphatase (BAP) and chondrex (CHON). The levels of cytokines IL-1 alpha, IL-8, IL-10 and TNF-alpha were assayed by immunoanalysis (ELISA and IMMULITE system) in BS, CA, SM, GT and SF. The tissue samples were obtained during arthroplasty. RESULTS: In the patients with osteoarthritis, the urinary levels of PYR and D-PYR were higher than control values (70.33 +/- 34.93 vs (41.6 +/- 10.6 nmol/mmol creatinine). No significant differences were found between pre- and post-operative levels. Similarly, the serum levels of BAP and CHON compared with control values were higher (27.65 +/- 12.21 vs 12.2 +/- 2.7 U/L and (96.35 +/- 58.83 vs 43.2 +/- 14.5 ng/ml, respectively). In all articular compartments and in synovial fluid, the level of cytokine IL-8 exceeded concentrations of the other cytokines. In blood serum, only IL-10 levels were markedly increased as against the control group (17.35 +/- 5.82 vs 9.80 +/- 4.40 pg/ml). DISCUSSION: Primary osteoarthritis is the most common joint disease that deteriorates with age. Its symptoms are pain and a lower range of motion in the joint affected. The initial involvement of articular cartilage progresses to degenerative changes involving synovial and bony structures. This degenerative disease gradually develops into an inflammatory disease. At this stage, osseous tissue shows an increase in metabolism and bone destruction results. In the control of inflammatory reactions by the immune system, cytokines, among other proteins, play an important role: some may enhance inflammation by activating leukocytes (IL-1, TNF-alpha, IL-8) while others, such as IL-10, have anti-inflammatory effects. CONCLUSION: During osteoarthritis, the articular compartment shows high metabolic processes that, in some patients, may increase and even persist some time after arthroplasty.

An immunohistochemical study of the dorsal capsule of the lumbar and thoracic facet joints.

STUDY DESIGN: The molecular composition of the extracellular matrix in the dorsal capsules of lumbar and thoracic facet joints was analyzed immunohistochemically. OBJECTIVES: To determine whether the immunohistochemical profile of the lumbar joint capsule suggests a role of the capsule in limiting axial rotation of the lumbar motion segment. SUMMARY OF BACKGROUND DATA: During axial rotation of the lumbar vertebrae, the axis of rotation shifts toward the facet joints in the direction of rotation. Thus, the capsule of the opposing joint should become tensed and wrap around the inferior articular process. Previous studies suggest that wrap-around ligaments are fibrocartilaginous. However, thoracic joint capsules are largely shielded from such loading and should be purely fibrous. METHODS: Dorsal capsules were removed from lumbar and thoracic facet joints of six adult cadavers. Specimens were immunolabeled with monoclonal antibodies for collagens, chondroitin, dermatan and keratan sulfates, versican, tenascin, aggrecan and link protein. Antibody binding was detected using the Vectastain ABC 'Elite' peroxidase kit (Vector Laboratories, Inc., Burlingame, CA). RESULTS: Both lumbar and thoracic joint capsules immunolabelled for most glycosaminoglycans and for Type I, III and VI collagens. However, labeling for Type II collagen, chondroitin-6-sulfate, aggrecan, and link protein was restricted to lumbar capsules. Such labeling was constantly seen at entheses and occasionally in the midsubstance. CONCLUSIONS: The molecular composition of the lumbar joint capsule suggests that it acts as a fibrocartilaginous, 'wrap-around' ligament that withstands compression in addition to tension during torsional movements of the lumbar spine. It wraps around the inferior articular process as rotation occurs and limits further movement.

Autonomic innervation of tendons, ligaments and joint capsules. A morphologic and quantitative study in the rat.

We analyzed the neuronal occurrence of autonomic transmitters; noradrenaline (NA), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), in the Achilles tendon, medial and lateral collateral ligaments and knee joint capsule in the rat--by immunohistochemistry (IHC). In addition, the tissue concentrations of the sympathetic neuropeptide, NPY, and the parasympathetic peptide, VIP, were determined by radioimmunoassay (RIA). IHC demonstrated nerve fibers containing sympathetic vasoconstrictors--NA and NPY--and the parasympathetic vasodilator, VIP, in all tissues. NPY- and NA-positive nerve fibers were predominantly observed in larger blood vessels, whereas, nerve fibers immunoreactive to VIP were found in smaller vessels. In many nerve fibers a co-localization of the transmitters was seen. RIA showed that the concentration of NPY compared to VIP was 15-times higher in ligaments and twice as high in tendons and capsules. The differences noted may reflect a difference in vulnerability to degenerative conditions. In pathological conditions, dysregulation of autonomic transmitters in hypovascularized tissues subjected to repetitive mechanical load may contribute to tissue hypoxia leading to degeneration and rupture of tendons and ligaments.

Sensory neuropeptidergic pattern in tendon, ligament and joint capsule. A study in the rat.

The normal occurrence of sensory neuropeptides in tendons, ligaments and joint capsules in the rat was analyzed by immunohistochemistry and radioimmunoassay (RIA). Nerve fibres immunoreactive to substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A, galanin and somatostatin were identified in the Achilles tendon as well as the collateral ligaments and joint capsule of the knee. The neuropeptidergic fibres were predominantly found in the epiligament and paratenon. However, SP- and CGRP-positive fibres were also seen in the proper ligament and tendon tissues. RIA showed higher concentrations of SP and CGRP in tendons than in ligaments and capsules. The morphological and quantitative data obtained on sensory neuropeptides in normal tendons, ligaments and joint capsules may be used as a reference for tissue analysis in painful and inflammatory conditions of the locomotor apparatus.

Cytokine receptor profile of arthroplasty macrophages, foreign body giant cells and mature osteoclasts.

In the arthroplasty pseudomembrane surrounding a loose prosthesis there is a marked macrophage and foreign body giant cell (FBGC) response to implant-derived wear particles. These cells contribute to the osteolysis of loosening by releasing cytokines and growth factors which influence the formation and activity of osteoclasts. Using a panel of monoclonal antibodies directed against known cytokine/growth factor receptors, we have determined by immunohistochemistry whether arthroplasty macrophages, FB-GCs and osteoclasts express receptors for cytokines and growth factors that are known to modulate osteolysis. All these cell types reacted with antibodies directed against the following cytokine/growth factor receptors: gp130, IL-1R type 1, IL-2R, IL-4R, IL-6R, TNFR, M-CSFR, GM-CSFR and SCFR but not with antibodies directed against IL-3R and IL-8R. Arthroplasty macrophages, FBGCs and osteoclasts thus show a similar pattern of cytokine/growth factor receptor expression. This reflects the fact that arthroplasty macrophages are capable of osteoclast differentiation and that these cell types form part of the mononuclear phagocyte system. As regards the osteolysis of aseptic loosening, it also indicates that these cells are targets for numerous cytokines and growth factors which influence osteoclast formation and bone resorption.

Analysis of collagen and elastic fibers in shoulder capsule in patients with shoulder instability.

This study examined collagen cross-links, collagen fibril diameter and density, amino acid composition, and elastic fibers in shoulder capsule and skin in four patient groups: 1) unidirectional anterior instability (N = 8); 2) multidirectional instability/primary surgery (N = 6); 3) multidirectional instability/revision surgery (N = 6); and 4) no history of instability (N = 5). Compared with normal capsule, capsule from groups 1 and 2 had more stable and reducible collagen cross-links, significantly greater mean collagen fibril diameter, more cysteine, and a higher density of elastin staining. Compared with shoulder capsule in groups 1 and 2, shoulder capsule from group 3 contained significantly more reducible cross-links, smaller-diameter collagen fibrils, decreased collagen fibril density, and an increased density of elastin staining. There were no significant differences in any parameters between groups 1 and 2. We hypothesized that repeated capsular deformation in patients with shoulder instability results in changes in the capsule that increase its strength and resistance to stretching. Skin analyses demonstrated a significantly smaller mean collagen fibril diameter in skin from group 2 compared with group 1, suggesting the possibility of an underlying connective tissue abnormality.

Electrothermally-assisted capsular shift.

The marriage of biomedical instrumentation and patient care has once again proven itself successful. The ETAC is a new procedure with various potential applications. Despite its embryonic stage, this procedure is being used by a handful of shoulder surgeons who are cautiously pursuing new and improved ways to prevent the common and debilitating diagnosis of shoulder instability. Follow-up thus far is short, and the current literature lacks studies that compare the time-honored conventional standard of open stabilization to this new procedure. However, those surgeons who have been using this device are optimistic about its role in the future repair of shoulder injuries.

The joint capsule and joint laxity in dogs with hip dysplasia.

Present knowledge of the complexity of joint diseases makes it difficult to investigate the causes and early pathogenesis of canine hip dysplasia. Clinical signs of canine hip dysplasia including joint laxity may be a result of primary or secondary alterations of the joint. We already know that joint laxity is related to effusive synovitis (ie, accumulation of synovial fluid) and to other primary collagenous diseases. Canine hip dysplasia may be a third collagenous disease associated with joint laxity. This paper summarizes some of the studies that investigated the relationship between joint laxity and a defect in collagen metabolism and the influence that alterations in transsynovial flow have on joint laxity.