Expression of immune response genes in the stifle joint of dogs with oligoarthritis and degenerative cranial cruciate ligament rupture

Dysregulation of immune responses within joints plays an important role in development of inflammatory arthritis. We determined expression of a panel of immune response and matrix turnover genes in synovial fluid collected from a group of dogs with stifle oligoarthritis and associated degenerative cranial cruciate ligament (CCL) rupture (n=27). We also studied synovial fluid gene expression in dogs affected with other forms of degenerative arthritis (n=9) and in the stifle joint of healthy dogs with intact CCL (n=14). After collection, synovial cells were pelleted and RNA was isolated. Relative expression of cathepsin K, cathepsin S, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), invariant chain (li), toll-like receptor-2 (TLR-2), and TLR-9 was determined using real-time quantitative RT-PCR. Data were normalized to peripheral blood mononuclear cells (PBMC) as an internal control. Relative expression of cathepsin K, MMP-9, TRAP, and li was increased in the stifle synovial fluid of dogs with oligoarthritis, when compared with the stifles of healthy dogs (P<0.05). In contrast, relative expression of all of the genes-of-interest in synovial fluid from joints affected with other forms of arthritis was not significantly different from the stifles of healthy dogs. TRAP expression was also significantly increased in the stifle joints of dogs with oligoarthritis, when compared to joint expression of TRAP in dogs with other forms of degenerative arthritis (P<0.05). In the dogs with stifle oligoarthritis, expression of both matrix turnover and immune response genes was increased in stifle synovial fluid, when compared with the internal PBMC control, whereas in healthy dogs and dogs with other forms of arthritis, only expression of matrix turnover genes was increased in synovial fluid, when compared with the internal PBMC control (P<0.05). Taken together, these findings suggest that antigen-specific immune responses within the stifle joint may be involved in the pathogenesis of persistent synovitis and associated joint degradation in dogs with oligoarthritis and degenerative CCL rupture.     

Feasibility of utilizing the patellar ligament angle for assessing cranial cruciate ligament rupture in dogs

The patellar ligament angle (PLA) was assessed in 105 normal stifle joints of 79 dogs and 33 stifle joints of 26 dogs with a ruptured cranial cruciate ligament (CrCL). The PLA of stifles with complete CrCL rupture was significantly lower than that of normal stifles, particularly at a flexion angle of 60~80° in both plain and stress views. If the PLA was <90.55° on the stress view with a 60~80° flexion angle, the dog was diagnosed with a complete rupture of the CrCL with a sensitivity of 83.9% and specificity of 100%. In conclusion, measuring the PLA is a quantitative method for diagnosing complete CrCL rupture in canines.     

Synovial fluid proteins in degenerative joint disease in dogs

Concentrations of three immunoglobulins, albumin, ceruloplasmin, alpha-2 macroglobulin and pregnancy zone protein were estimated by immunoelectrophoresis in paired samples of synovial fluid and serum from 12 dogs with degenerative joint disease (DJD) and six normal dogs. The ratios of synovial fluid to serum concentrations (SF/S) of the four non-immunoglobulins showed an almost inverse linear relationship with their molecular weight in both groups. The SF/S were higher in the DJD synovial fluid than in normal synovial fluid. The difference increased with increasing molecular weight and was highly significant for the largest molecules, reflecting an increased permeability and inflammation in the synovial membrane of DJD joints. The SF/S ratios of the three immunoglobulins studied were compared to the diffusion curves of the four non-immunoglobulins. The SF/S ratios of IgM from dogs with DJD exceeded those calculated from the molecular weights. The present observations support the concept that DJD should be considered an inflammatory disease and suggest that immunologic processes may initiate and/or sustain the inflammation.     

Apoptosis of ligamentous cells of the cranial cruciate ligament from stable stifle joints of dogs with partial cranial cruciate ligament rupture

OBJECTIVE: To describe the presence and amount of apoptotic ligamentous cells in different areas of partially ruptured canine cranial cruciate ligaments (prCCLs) and to compare these findings with apoptosis of ligamentous cells in totally ruptured cranial cruciate ligaments (trCCLs). ANIMALS: 20 dogs with prCCLs and 14 dogs with trCCLs. PROCEDURES: Dogs with prCCLs or trCCLs were admitted to the veterinary hospital for stifle joint treatment. Biopsy specimens of the intact area of prCCLs (group A) and the ruptured area of prCCLs (group B) as well as specimens from trCCLs (group C) were harvested during arthroscopy. Caspase-3 and poly (ADP-ribose) polymerase (PARP) detection were used to detect apoptotic ligamentous cells by immunohistochemistry. RESULTS: No difference was found in the degree of synovitis or osteophytosis between prCCLs and trCCLs. No difference was found in degenerative changes in ligaments between groups A and B. A substantial amount of apoptotic cells could be found in > 90% of all stained slides. A correlation (r(s) = 0.71) was found between the number of caspase-3-and PARP-positive cells. No significant difference was found in the amount of apoptotic cells among the 3 groups. No significant correlation could be detected between the degree of synovitis and apoptotic cells or osteophyte production and apoptotic cells. CONCLUSIONS AND CLINICAL RELEVANCE: The lack of difference between the 3 groups indicates that apoptosis could be a factor in the internal disease process leading to CCL rupture and is not primarily a consequence of the acute rupture of the ligament.     

Synovitis in dogs with stable stifle joints and incipient cranial cruciate ligament rupture: a cross-sectional study

Objective: To evaluate stifle joints of dogs for synovitis, before development of joint instability and cranial cruciate ligament rupture (CrCLR). Study Design: Cross‐sectional study. Animals: Dogs (n=16) with CrCLR and stable contralateral stifles; 10 control dogs with intact CrCL. Methods: Arthritis and tibial translation were graded radiographically. Synovitis severity and cruciate pathology were assessed arthroscopically. Presence of inflammatory cells in synovial membrane biopsies was scored histologically. CrCLR stifle pairs and control stifles were compared. Results: Radiographic evidence of arthritis, cranial tibial translation, and arthroscopic synovitis were increased in unstable stifles, when compared with stable contralateral stifles in CrCLR dogs (P<.05). Arthroscopic synovitis in both joints of CrCLR dogs was increased compared with controls, was correlated with radiographic arthritis (S_R=0.71, P<.05), and was present in all stable contralateral stifles. Arthroscopically, 75% of stable stifle joints had CrCL fiber disruption, which correlated with severity of synovitis (S_R=0.56, P<.05). Histologic evidence of synovitis was identified in all CrCLR dogs, but was only significantly correlated with arthroscopic observations in stable stifles (r²=0.57, P<.005). Conclusion: Synovitis is an early feature of the CrCLR arthropathy in dogs before development of joint instability clinically. Severity of synovitis is correlated with radiographic arthritis in joints with minimal to no clinically detectable CrCL damage.     

Radiographic measurement of craniocaudal instability in stifle joints of clinically normal dogs and dogs with injury of a cranial cruciate ligament

OBJECTIVE: To determine craniocaudal laxity of the stifle joint of dogs when joints were positioned in tibial compression or neutral position. SAMPLE POPULATION: 19 normal stifle joints in 10 clinically normal dogs, 29 stifle joints with varying injury to the cranial cruciate ligament (10 complete ruptures alone, 10 complete ruptures with concomitant damage to the medial meniscus, 6 partial ruptures alone, and 3 partial ruptures with concomitant meniscal tearing), and 19 unaffected contralateral stifle joints in those 29 dogs. PROCEDURE: Relative displacement of bony landmarks was measured on paired lateral radiographs (neutral and tibial compression positions). Two measuring techniques were customized for use in dogs. RESULTS: The first technique failed to distinguish results in normal stifle joints from those in stifle joints with partial deficiency of cranial cruciate ligaments. Significant differences were found for joints with complete rupture, compared with stifle joints in clinically normal dogs. The second technique detected differences between normal stifle joints and injured joints with partial or complete rupture of the cranial cruciate ligament. Significant differences were not detected between joints with partial versus complete rupture. Adjusting data to account for size of dog did not improve results. CONCLUSIONS AND CLINICAL RELEVANCE: A wide range in measurements of laxity was found for stifle joints with intact cranial cruciate ligaments. Differences in degree of damage to the ligament and medial meniscus cannot be deduced from the amount of relative displacement measured on radiographs. Pathologic changes to the cranial cruciate ligament will not necessarily induce detectable changes in laxity of stifle joints in dogs.     

Deep learning-based diagnosis of stifle joint diseases in dogs

In this retrospective, analytical study, we developed a deep learning-based diagnostic model that can be applied to canine stifle joint diseases and compared its accuracy with that achieved by veterinarians to verify its potential as a reliable diagnostic method. A total of 2382 radiographs of the canine stifle joint from cooperative animal hospitals were included in a dataset. Stifle joint regions were extracted from the original images using the faster region-based convolutional neural network (R-CNN) model, and the object detection accuracy was evaluated. Four radiographic findings: patellar deviation, drawer sign, osteophyte formation, and joint effusion, were observed in the stifle joint and used to train a residual network (ResNet) classification model. Implant and growth plate groups were analyzed to compare the classification accuracy against the total dataset. All deep learning-based classification models achieved target accuracies exceeding 80%, which is comparable to or slightly less than those achieved by veterinarians. However, in the case of drawer signs, further research is necessary to improve the low sensitivity of the model. When the implant group was excluded, the classification accuracy significantly improved, indicating that the implant acted as a distraction. These results indicate that deep learning-based diagnoses can be expected to become useful diagnostic models in veterinary medicine.     

Radiographic assessment of the progression of osteoarthrosis in the contralateral stifle joint of dogs with a ruptured cranial cruciate ligament

The formation and progression of osteoarthrosis in the unaffected contralateral stifle joints of 14 dogs with a unilateral cranial cruciate ligament rupture were monitored radiographically in terms of a global score and the scores for 10 parameters specific for the stifle joint. The dogs were examined initially and six and 12 months later by three observers, and the variability between the observers' scores was also assessed. The score for osteophytes at the tibial attachment site of the ligament was the most reliable parameter, and that for the increase in femoropatellar joint space was the least reliable. In the contralateral stifle joints there were significant increases after six and 12 months in osteophyte formation caudal to the tibial plateau, and in subchondral sclerosis of the tibial plateau and of the long digital extensor muscle groove. These three parameters progressed more regularly during the disease process than the other parameters. The global osteoarthrosis score of the contralateral stifle joint was an important risk factor for sustaining a rupture of the cranial cruciate ligament in that joint during the next six months.     

Changes in the canine stifle joint following rupture of the anterior cruciate ligament

Sixty–four dogs with rupture of the anterior cruciate ligament in one or both stifle joints were referred to the Royal Veterinary College, London for treatment. Details of the pathological changes in the joints were recorded at the time of open surgery in fifty–seven and these changes are discussed. A post–mortem examination was made on one dog and the joint lesions were studied more closely.     

Clinically significant,nontraumatic, degenerative joint disease of the temporomandibular joints in a horse

Horses with degenerative joint disease (DJD) of the temporomandibular joint (TMJ) have been reported infrequently, with the majority of cases describing the disease as a consequence of an earlier traumatic event. A case of clinically significant TMJ‐DJD due to a nontraumatic event has not been published. This retrospective case report describes a case of bilateral, DJD of the TMJ. Case management, subsequent review and interpretation of the clinical records, tangential radiographic views of each TMJ, computed tomography and magnetic resonance imaging of the head, and post mortem histological examination of the TMJs were performed. The horse exhibited both quidding and a ‘clicking’ sound during mastication; episodes of intermittent colic were also prevalent in the horse's history. Computed tomography illustrated bilateral mineralisation of the rostral aspect of both intra‐articular discs. Treatment, by intra‐articular injection of corticosteroid, resulted in temporary resolution of both the quidding and the ‘clicking’ sound, as well as the recurrent episodes of colic. Repeated treatment over time was required. Ultimately the horse was subjected to euthanasia for reasons other than disease of the TMJ. The development of TMJ‐DJD may not be confined to traumatic events. Age‐related degeneration of this joint may occur and manifest through quidding and abnormal sounds noted during mastication.     

Evaluation of anticollagen type I antibody titers in synovial fluid of both stifle joints and the left shoulder joint of dogs with unilateral cranial cruciate disease

OBJECTIVE: To evaluate anticollagen type I antibodies in synovial fluid of the affected stifle joint, the contralateral stifle joint, and the left shoulder joint of dogs with unilateral cranial cruciate ligament (CrCL) rupture during an extended period of 12 to 18 months. ANIMALS: 13 client-owned dogs with CrCL rupture and 2 sham-operated dogs. PROCEDURES: All dogs were examined and arthrocentesis of all 3 joints was performed every 6 months after surgery. Synovial fluid samples were tested for anticollagen type I antibodies by use of an ELISA. RESULTS: Dogs with partial CrCL rupture had higher antibody titers than dogs with complete rupture. Six of 13 dogs ruptured the contralateral CrCL during the study, whereby higher antibody titers were found for the stifle joints than for the shoulder joint. Seronegative dogs or dogs with extremely low antibody titers and 2 dogs with high antibody titers did not sustain a CrCL rupture in the contralateral stifle joint. CONCLUSIONS AND CLINICAL RELEVANCE: In most dogs that had a CrCL rupture of the contralateral stifle joint, a distinct antibody titer gradient toward the stifle joints was detected, suggesting that there was a local inflammatory process in these joints. However, only a small number of sham-operated dogs were used to calculate the cutoff values used to determine the anticollagen type I antibody titers in these patients. Synovial fluid antibodies against collagen type I alone do not initiate CrCL rupture because not all dogs with high antibody titers sustained a CrCL rupture in the contralateral stifle joint.     

The canine stifle joint I. Rupture of the anterior cruciate ligament

A method of assessment of cases of rupture of the anterior cruciate ligament with a view to prescribing either surgical or conservative treatment is described. The results of treatment of the cases after such an assessment indicates that the majority of small dogs will recover to satisfactory function after 2 months enforced rest, but large breed and working dogs require surgical intervention for successful treatment.
Résumé. Les auteurs décrivent une méthode propre à évaluer les ruptures du ligament cruci-forme antérieur en vue de prescrire soit l'intervention chirurgicale, soit le traitement conserva-teur. Les résultats thérapeutiques obtenus sur la base de cette évaluation portent à conclure que chez le chien de petite taille, 2 mois de repos forcé permettent le plus souvent d'obtenir un rétablissement fonctionnel satisfaisant, tandis que chez les chiens de grande taille et chiens d'utilité, l'intervention chirurgicale s'impose.
Zusammenfassung. Es wird eine Methode zur klinischen Beurteilung von Fällen einer Ruptur des vorderen Kreuzbandes im Hinblick auf die Möglichkeit einer chirurgischen oder konservativen Behandlung beschrieben. Die Behandlungsergebnisse bei den Fällen nach einer solchen Beurteilung zeigen, dass die Mehrzahl von kleinen Hunden sich in 2 Monaten Zwangsruhe zu einer zufriedenstellenden Funktion erholt, grosse Rassen und Arbeitshunde aber einen chirurgischen Eingriff zur erfolgreichen Behandlung benötigen.     

Radiographic and clinical survey of degenerative joint disease in the distal tarsal joints in Icelandic horses

The prevalence of degenerative joint disease (DJD) in the distal tarsal joints and the relation between radiographic and clinical signs compatible with the disease were estimated in a population of Icelandic horses used for riding. The material consisted of 614 horses age 6-12 years (mean age = 7.9 years). Radiographs with 3 projections of each tarsus were made and a clinical examination, including palpation of the medial aspect of the distal tarsus and motion evaluation of the hindlimbs before and after a flexion test of the tarsus, was performed. Radiographic signs of DJD in the distal tarsal joints were found in 30.3% of the horses and the prevalence was strongly correlated with age. Hindlimb lameness before and after flexion test and palpation abnormalities were significantly associated with the radiographic findings. The lameness was usually mild and, in most cases, detectable only after the flexion test. The prevalence of lameness was not significantly correlated with age. Lameness could not be predicted by details of the radiographic findings.     

Evaluation of the Norberg angle threshold: a comparison of Norberg angle and distraction index as measures of coxofemoral degenerative joint disease susceptibility in seven breeds of dogs

OBJECTIVE: To evaluate the thresholds of 2 radiographic methods used to determine coxofemoral joint laxity in 7 breeds of dogs. ANIMALS: Three hundred and fifty clinically normal dogs. STUDY DESIGN: Retrospective study. METHODS: Hip radiographs from 7 breeds of dogs were randomly selected from a database. None of the dogs had radiographic evidence of degenerative joint disease (DJD). Distraction index (DI) and Norberg angle (NA) were measured on these radiographs and compared with DI and NA thresholds for diagnosing DJD susceptibility derived from the literature and from evaluated Borzois. Dogs with a NA<105 degrees and a DI of < or =0.32 were considered false-positives and dogs with a NA> or =105 degrees and a DI of >0.32 were considered false-negatives. RESULTS: Mean age of all dogs was 22.9 months. Mean NA for all dogs was 99.37 degrees, and mean DI for all dogs was 0.44. Borzoi mean DI of was significantly less than the mean DI of the other 6 breeds. The highest (most hip laxity) Borzoi DI was 0.32, and the lowest (most hip laxity) Borzoi NA was 99 degrees. False-positive and false-negative diagnoses were identified in 6 of the 7 breeds. CONCLUSIONS: Using the NA threshold of 105 degrees (literature established threshold of susceptibility to DJD) resulted in a high percentage of false-negative and false-positive diagnoses. Breeds like the Labrador Retriever and Rottweiler would have large numbers of hip dysplasia susceptible dogs remain in the breeding population based on this NA threshold. False-positive diagnoses were common in breeds like the Australian Shepherd, Borzoi, and German Shepherd effectively eliminating hip dysplasia nonsusceptible dogs from the breeding population. CLINICAL RELEVANCE: The NA was not an accurate predictor of DJD susceptibility in these 7 breeds of dogs when using a NA threshold of 105 degrees.     

A degenerative joint disease in the horse

Extract

Osteochondritis dissecans has been reported in most of the domestic species and, in particular, in those breeds within the species where the emphasis has been on selection for large size and rapidmaturity. It is seen most commonly on the epiphysis forming the main weight-bearing joints, the shoulder, elbow, hip, stifle and hock. In the horse the most commonly affected joint is the femero-patellar joint with the lesion occurring at the same site at approximately the mid-point of the lateral trochlear ridge. This paper is confined to a discussion of this condition.