Adipocytes in synovial fluid cytology: An approach for diagnosing synovial lipomatosis.

A 2-year-old neutered male bullmastiff dog was presented with chronic left hind limb lameness. Physical examination revealed left stifle effusion and medial buttress without cranial tibial thrust. Radiographs showed joint effusion and new bone formation at the patella apex. Magnetic resonance imaging showed increased synovial fluid, widening of the joint space, abnormal infrapatellar fat body and thinning of the cranial cruciate ligament. Synoviocentesis and cytologic evaluation of synovial fluid revealed marked mononuclear inflammation with abundant fatty tissue, suggesting synovial lipomatosis in conjunction with the imaging findings. The disease was confirmed histologically after sampling the lesion during arthrotomy. Synovial lipomatosis, characterized by extensive synovial adipose tissue proliferation of the synovial membrane, is a rare "tumor-like" disorder that usually affects the stifle. Although the etiology remains unclear, joint trauma, inflammation, instability, and lipid abnormalities have been proposed as causes. Inflammatory factors may promote synoviocyte and adipocyte hyperplasia that perpetuate the process. Surgical removal may be suggested to eliminate triggers and prevent future recurrences. The report provides the first cytological description of adipocytes in synovial fluid associated with the diagnosis of synovial lipomatosis in dogs. This case report underscores the potential effectiveness of cytologic analysis of synovial fluid smears, in combination with magnetic resonance imaging (MRI), for diagnosing this condition and reducing complications associated with arthrotomy for sampling purposes. Additionally, the case highlights that synovial lipomatosis should be considered as a potential differential diagnosis for synovial masses in dogs. Further cases are needed to validate these observations in veterinary medicine.

No correlation found between palpation and ultrasound for evaluation of effusion in the medial femorotibial and femoropatellar joint compartments of horses.

OBJECTIVE: To compare palpation and ultrasound scores of effusion of the medial femorotibial and femoropatellar joints of horses. ANIMALS: 40 horses (80 stifles) were evaluated over a 12-week period. METHODS: Horses > 1 year of age without history of stifle disease were enrolled from September to December 2022. Palpation of right and left medial femorotibial and femoropatellar joint compartments was performed. Amount of effusion was scored by a board-certified large animal surgeon, a third-year large animal surgery resident, and an equine sports medicine intern. Effusion of right and left medial femorotibial and femoropatellar joints was quantified with ultrasound by a board-certified equine sports medicine and rehabilitation clinician. Amount of effusion on palpation and ultrasound was graded as none-mild (1), moderate (2), or severe (3). A 2-way intraclass correlation coefficient evaluated interrater reliability of palpation scores. The Spearman rank correlation determined association between palpation and ultrasound scores. RESULTS: Interrater reliability for palpation of effusion was poor between all observers for all joint compartments. No significant correlation was identified between palpation and ultrasound scores for any joint compartment for any observer. CLINICAL RELEVANCE: Clinicians often rely on palpation of joint effusion as an indication of stifle pathology. We found interrater reliability to be poor for palpation scores, indicating low agreement for palpation of joint effusion between clinicians within our group. No correlation was found between palpation and ultrasound scores for joint effusion, indicating that clinicians should not rely on palpation alone to quantify joint effusion of the medial femorotibial and femoropatellar joints.

Computed tomographic imaging and surgical management of distal insertional avulsion fragments of the caudal cruciate ligament in four horses.

OBJECTIVE: To describe cases with caudal cruciate ligament (CdCL) avulsion fragments diagnosed based on computed tomography (CT) examination and report on arthroscopic fragment removal. ANIMALS: Four Warmblood horses with hindlimb lameness and osseous fragments located in the caudal medial femorotibial joint (mFTJ). STUDY DESIGN: Short case series. METHODS: CT and arthroscopic evaluation of the caudal mFTJ were performed. The caudal mFTJ and the insertion of the CdCL on the tibia were assessed and removal of the avulsion fragments was attempted in three horses using a cranial intercondylar approach. RESULTS: The fragment was not accessible via caudomedial approaches in one horse. A cranial intercondylar approach was used in three horses, allowing removal of the intra-articular fragment in two horses, and removal of two-thirds of the proximal fragment in the last horse. Acute, profuse, arterial bleeding occurred in this horse during surgery with transient postoperative soft tissue swelling. Comorbidities included medial femoral condyle cartilage defects (3), cranial cruciate ligament lesions (2), and medial collateral ligament lesions (2). Horses were followed up for 16 months (median, range 11-28 months), at which point all were back in ridden exercise; owners' satisfaction was good. CONCLUSION: CT examination confirmed the diagnosis and allowed evaluation of the stifle joint for comorbidities. A cranial intercondylar arthroscopic approach facilitated the removal of CdCL insertional avulsion fragments, although not always complete. CLINICAL SIGNIFICANCE: A cranial intercondylar approach can allow access to CdCL avulsion fragments, but complications and incomplete removal remain possible.

Arthroscopic Caudal Cruciate Ligament Damage in Canine Stifles with Cranial Cruciate Ligament Disease.

OBJECTIVE: The aim of this study was to describe the arthroscopic changes to the caudal cruciate ligament (CdCL) in dogs with cranial cruciate ligament disease. STUDY DESIGN: Arthroscopic video recordings (n = 117) of the stifle with cranial cruciate ligament disease were reviewed. The extent of CdCL tearing was described. Signalment, palpable stifle stability and the presence of a meniscal tear were recorded. Pathology of the synovial joint and the synovium overlying the CdCL were scored at two time points.Two-way interactions were investigated (p < 0.05). Univariate analysis and a Wald test (p < 0.20) were performed. Factors were retained with a Wald test p < 0.05 or if a confounder, then a changing model coefficient >15%. A weighted kappa statistic was used to evaluate intraobserver agreement. RESULTS: Caudal cruciate ligament tearing was identified in 94% of stifles. Longitudinal tearing (76%) was the most common type of damage (45% partial, 31% full thickness). Synovitis was present in all joints and changes to the synovium overlying the CdCL were less frequently identified (67%).Synovitis was associated with the degree to CdCL tearing. Synovitis overlying the CdCL was associated with lower body weight and lower CdCL damage. CONCLUSION: Caudal cruciate ligament damage is common in dogs with cranial cruciate ligament disease and longitudinal tearing was the most common injury identified. Severity of joint pouch synovitis was positively correlated with the degree of CdCL damage and the portion of the CdCL not exposed to the synovium was unaffected. These findings suggest synovitis is likely a contributor to CdCL injury.

Comparison of Two Stifle Exploratory Methods Using Mini-Arthrotomy for Diagnosis of Canine Medial Meniscal Pathology: An Ex Vivo Study.

OBJECTIVE: The main aim of this study was to compare the accuracy of stifle exploratory using either a stifle distractor (SD method) or a combination of Hohmann and Senn retractors (HS method) for diagnosing canine medial meniscal tears in cranial cruciate ligament-deficient stifles. STUDY DESIGN: Fifteen pairs of canine cadaveric pelvic limbs were used and cranial cruciate ligament were transected in all stifles. Paired limbs were then randomly assigned to one of five groups based on the tears created in the caudal pole of the medial meniscus: no tear, peripheral detachment, or a variation in three vertical longitudinal tears. A craniomedial mini-arthrotomy was performed by two observers and diagnosis of the medial meniscal status was made utilizing the HS and SD methods. Correct diagnosis of the meniscal tear was compared for both methods and observers. RESULTS: Correct diagnoses were made using the HS and SD methods in 24/30 and 24/30 cases for observer 1 respectively; and in 17/30 and 19/30 cases for observer 2 respectively. There was no significant difference in the correct diagnosis of meniscal tears within each observer between the two methods. CONCLUSION: Both HS and SD methods have equal accuracy for the diagnosis of canine medial meniscal pathology for a board-certified surgeon. Unassisted surgeons using the SD method for the evaluation of the medial meniscus are at no diagnostic disadvantage compared with assisted surgeons utilizing the HS method.

Arthroscopic findings and long-term outcomes in 76 sport horses with meniscal injuries (2008-2018).

OBJECTIVE: To report the findings and long-term outcome of 76 sport horses with meniscal injury. STUDY DESIGN: Retrospective case series. ANIMALS: Seventy-six horses with 93 meniscal injuries in 85 stifles. METHODS: Medical records of sport horses diagnosed with meniscal injury during arthroscopy were reviewed. Owner follow up was obtained via telephone interview ≥1.5 years postoperatively. Preoperative and intraoperative findings, and postoperative treatments, were analyzed for potential association with return to athletic performance. RESULTS: The medial meniscus was involved in 82.8% of cases, with grade 1 injuries diagnosed in 76.3% of menisci. Overall, 85.5% of horses returned to athletic performance, with 40% returning to their previous level. The grade of meniscal injury was associated with long-term outcome (P = .023). The presence of preoperative radiographic abnormalities (P = .259) or additional joint pathology (P = 1.00) was not associated with long-term outcomes. Fifty-nine stifles were treated with an orthobiologic: autologous conditioned serum, platelet-rich plasma, or marrow-derived mesenchymal stem cells. There was no association between the use of any orthobiologic and long-term outcome (P = .394). CONCLUSION: This is the first report on long-term outcome of sport horses with meniscal injuries following arthroscopic surgery. Overall, the long-term prognosis was fair, with 40% of horses returning to their previous level of use. Severity of the meniscal injury was a prognostic indicator for return to work. The presence of radiographic abnormalities or additional joint pathology, or the use of orthobiologics, was not associated with long-term outcome. CLINICAL SIGNIFICANCE: These findings can help in prognostication for sport horses with meniscal injuries.

Synovial and cartilage responsiveness to peri-operative hyaluronic acid ± dexamethasone administration following a limited injury to the rabbit stifle joint.

Posttraumatic osteoarthritis (PTOA) can develop after an injury to the knee. Previous studies have indicated that an intra-articular (IA) injection of the potent glucocorticoid dexamethasone (DEX) may significantly prevent induction of PTOA. The aim of the present study was to investigate the effectiveness of a single IA injection of hyaluronic acid (HA), alone and in combination with DEX following a localized intra-articular injury as a PTOA-preventing treatment option. An established rabbit model of surgical injury consisting of dual intra-articular (IA) drill holes in a non-cartilaginous area of the femoral notch near the origin of the anterior cruciate ligament (ACL) to allow for bleeding into the joint space was used. Immediately following surgery, subjects were treated with HA, HA + DEX, or received no treatment. An uninjured control group was used for comparison (N = 5/group). Rabbits were sacrificed and investigated at 9 weeks post-injury. At 9 weeks post-injury, there was a significant protective capacity of the single IA treatment of DEX + HA on the histological grade of the synovial tissue, and some variable location-specific effects of HA alone and HA + DEX interactions on cartilage damage. Thus, it is possible that co-treatment with HA may interfere with the effectiveness of the DEX. In vitro friction testing indicated that DEX did not interfere with the lubricating ability of HA or synovial fluid on cartilage. These results suggest that a single IA administration of HA in combination with DEX following an IA injury is not recommended for inhibition of PTOA progression in this model.

Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

Effects of long-term exercise and a high-fat diet on synovial fluid metabolomics and joint structural phenotypes in mice: an integrated network analysis.

OBJECTIVE: To explore how systemic factors that modify knee osteoarthritis risk are connected to 'whole-joint' structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. METHODS: Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9-13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. RESULTS: High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1ß and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. CONCLUSION: Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.

A single dose of anti-IL-1ß antibodies prevents Western diet-induced immune activation during early stage collagenase-induced osteoarthritis, but does not ameliorate end-stage pathology.

OBJECTIVE: Metabolic dysfunction can cause IL-1ß mediated activation of the innate immune system, which could have important implications for the therapeutic efficacy of IL-1ß neutralizing drugs as treatment for OA in the context of metabolic syndrome (MetS). In the present study, we investigated whether early treatment with a single dose of IL-1ß blocking antibodies could prevent Western diet (WD) induced changes to systemic monocyte populations and their cytokine secretion profile and herewith modulate collagenase induced osteoarthritis (CiOA) pathology. METHODS: CiOA was induced in female C57Bl/6 mice fed either a standard diet (SD) or WD and treated with a single dose of either polyclonal anti-IL-1ß antibodies or control. Monocyte subsets and granulocytes in bone marrow and blood were analyzed with flow cytometry, and cytokine expression by bone marrow cells was analyzed using qPCR. Synovial cellularity, cartilage damage and osteophyte formation were assessed on histology. RESULTS: WD feeding of C57Bl/6 mice led to increased serum levels of low-density lipoprotein (LDL) and innate immune activation in the form of an increased number of Ly6Chigh cells in bone marrow and blood and increased cytokine expression of IL-6 and TNF-α by bone marrow cells. The increase in monocyte number and activity was ameliorated by anti-IL-1ß treatment. However, anti-IL-1ß treatment did not significantly affect synovial lining thickness, cartilage damage and ectopic bone formation during WD feeding. CONCLUSIONS: Single-dose systemic anti-IL-1ß treatment prevented WD-induced innate immune activation during early stage CiOA in C57Bl/6 mice, but did not ameliorate joint pathology.

Pathology-pain relationships in different osteoarthritis animal model phenotypes: it matters what you measure, when you measure, and how you got there.

OBJECTIVE: To determine whether osteoarthritis (OA) pain characteristics and mechanistic pathways in pre-clinical models are phenotype-specific. DESIGN: Male 11-week-old C57BL6 mice had unilateral medial-meniscal-destabilization (DMM) or antigen-induced-arthritis (AIA), vs sham-surgery/immunised-controls (Sham/Im-CT). Pain behaviour (allodynia, mechanical- and thermal-hyperalgesia, hindlimb static weight-bearing, stride-length) and lumbar dorsal root ganglia (DRG) gene-expression were measured at baseline, day-3, week-1/-2/-4/-8/-16, and pain-behaviour:gene-expression:joint-pathology associations investigated. RESULTS: DMM and AIA induced structural OA defined by progressively increasing cartilage erosion, subchondral bone sclerosis and osteophyte size and maturation. All pain-behaviours were modified, with model-specific differences in severity and temporal pattern. Tactile allodynia developed acutely in both models and persisted to week-16. During early-OA (wk4-8) there was; reduced right hindlimb weight-bearing in AIA; thermal-hyperalgesia and reduced stride-length in DMM. During chronic-OA (wk12-16); mechanical-hyperalgesia and reduced right hindlimb weight-bearing were observed in DMM only. There were no associations in either model between different pain-behaviour outcomes. A coordinated DRG-expression profile was observed in sham and Im-CT for all 11 genes tested, but not in AIA and DMM. At wk-16 despite equivalent joint pathology, changes in DRG-expression (Calca, Trpa1, Trpv1, Trpv4) were observed only in DMM. In AIA mechanical-hyperalgesia was associated with Trpv1 (r = -0.79) and Il1b (r = 0.53). In DMM stride-length was associated with Calca, Tac1, Trpv1, Trpv2, Trpv4 and Adamts5 (r = 0.4-0.57). DRG gene-expression change was correlated with subchondral-bone sclerosis in DMM, and cartilage damage in AIA. Positive pain-behaviour:joint-pathology associations were only present in AIA - for synovitis, subchondral-bone resorption, chondrocyte-hypertrophy and cartilage damage. CONCLUSION: Pain and peripheral sensory neuronal responses are OA-phenotype-specific with distinct pathology:pain-outcome:molecular-mechanism relationships.

An LC-MS/MS method for simultaneous quantification of 11 components of Xian-Xiong-Gu-Kang in the plasma of osteoarthritic rats and pharmacokinetic analysis.

Xian-Xiong-Gu-Kang is composed of Epimedium brevicornu, Ligusticum chuanxiong, Radix clematidis, Cinnamomum cassia, and Fructus xanthii. It is used to treat numbness and pain of limbs. In this study, we developed a method to simultaneously quantify 11 components of Xian-Xiong-Gu-Kang (icarrin, epimedin A, epimedin B, epimedin C, icariside II, chlorogenic acid, ligustilide, senkyunolide A, senkyunolide I, ferulic acid, and cinnamic acid) in rat plasma using ultra-performance liquid chromatography coupled with quadrupole linear ion trap mass spectrometry. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column using gradient elution with a mobile phase comprising acetonitrile and 0.05% (v/v) formic acid aqueous solution. Mass spectrometry detection was performed using positive and negative electrospray ionization in the multiple reaction monitoring mode. The calibration curves of the 11 constituents were linear, with correlation coefficients > 0.99. The intra- and interday accuracy and precision values were within ±15.0%. The extraction recoveries of the 11 constituents and two internal standards were between 66.05 and 105.40%, and the matrix effects were between 86.74 and 112.86%. Using this method, the pharmacokinetic features of the 11 constituents were elucidated in the plasma of osteoarthritic rats after oral administration of the Xian-Xiong-Gu-Kang extract.

The epidemiology of stifle joint disease in an insured Swedish dog population.

BACKGROUND: Stifle joint diseases (SJD) are common in dogs and include a variety of diagnoses. The objective of the study was to provide an overview of the epidemiology of SJD in insured dogs. METHODS: An historical single cohort study of dogs insured in Agria Pet Insurance (2011-2016) in Sweden was performed. Incidence and relative risk (RR) of SJD was calculated for the whole dog population and for subgroups divided by breed, breed group and sex. RESULTS: The study population included almost 600,000 insured dogs (>1.7 million dog-years). Ninety-three different stifle joint diagnoses were reported in 9624 dogs, and the most common were cruciate ligament rupture and patellar luxation. The incidence of SJD was 55.4 cases per 10,000 dog-years at risk. Bulldog and boerboel had the highest RR of SJD. The breeds that accounted for the highest proportion of all SJD claimed dogs were mixed breed and Labrador retriever. Female dogs had a slightly increased RR compared with male dogs (RR 1.06, p = 0.006). The incidence increased yearly during the observation period. CONCLUSION: The study demonstrates breed-specific differences in incidence of SJD in dogs, which may be of importance for breeders, dog owners and veterinarians.

Comparison of joint degeneration and pain in male and female mice in DMM model of osteoarthritis.

OBJECTIVE: While the prevalence of radiographic and symptomatic osteoarthritis (OA) is higher in women, male mice are more frequently used in animal experiments to explore its pathogenesis or drug efficacy. In this study, we examined whether sexual dimorphism affects pain and joint degeneration in destabilization of the medial meniscus (DMM) mouse model. METHODS: DMM or sham surgery was performed on the knee of male and female C57BL/6 mice. Joint damage was assessed by safranin O staining and scored using the Osteoarthritis Research Society International (OARSI) scoring system. Von Frey hair, incapacitance, and rotarod tests were conducted to measure joint pain. The analgesic effect of capsazepine (CPZ), a TRPV1 antagonist, was compared between male and female mice. RESULTS: Histology and OARSI scoring analysis showed that cartilage degeneration developed, and progressed in both male and female DMM groups, however, damage was less severe in females at the late stage of OA. Pain behavior, as measured by mechanical allodynia, was displayed for longer in male DMM mice compared to females. Incapacitance data showed that CPZ significantly reduced DMM-induced pain in male mice but not in female mice. Immunofluorescence microscopy analysis demonstrated that DMM surgery increased the expression of TRPV1 in both female and male dorsal root ganglion (DRG). Injection of CPZ significantly suppressed TRPV1 expression in the DRG of male mice only. CONCLUSION: Joint damage develops comparably in both female and male mice after DMM although it progresses less in females. There was a subtle sex difference in pain behaviors and analgesic efficacy of a TRPV1 antagonist, which was accompanied by a differential regulation of TPRV1.

Optimization of histologic grading schemes in spontaneous and surgically-induced murine models of osteoarthritis.

OBJECTIVE: To compare the Osteoarthritis Research Society International (OARSI) and Articular Cartilage Structure (ACS) grading schemes applied to multiple and single sections, along with additional histologic measures, in two mouse models of Osteoarthritis (OA). METHODS: Six coronal histologic stifle joint sections were collected from 40 C57BL/6J mice, including aged mice with spontaneous OA (approximately 18 months of age; n = 15) and young (12-week-old) mice that either underwent destabilization of the medial meniscus (DMM) surgery (n = 15) or sham surgery (n = 10). Sections were evaluated with the standard OARSI (0-6) scheme, a modified OARSI scheme, the ACS (0-12) scheme, histomorphometry of cartilage and bone, and scoring of osteophytes (0-3) and synovial hyperplasia (0-3). Principal components analysis (PCA) was used to determine the features explaining the greatest variability among the sections. RESULTS: The grading schemes performed similarly when applied to a single mid-coronal section or six total coronal sections per joint. OARSI grading produced similar results when applied to hematoxylin and eosin or toluidine blue-stained sections. Aged mice had higher severity scores in the LTP than DMM mice (mid-coronal OARSI grade aged = 2.3 and DMM = 1.1, p = 0.0006; ACS grade aged = 4.1 and DMM = 1.6, p = 0.0024). PCA resulted in retention of four factors that accounted for 78.4% of the total variance. Factor 1 (36.4%) included the OARSI grade, ACS grade, Toluidine blue grade, articular cartilage area and thickness and the osteophyte grade. CONCLUSIONS: Grading of a single mid-coronal section using either the OARSI or ACS schemes combined with osteophyte and histomorphometric measures can consistently define OA severity in mice.

Variations in gene expression levels with severity of synovitis in dogs with naturally occurring stifle osteoarthritis.

Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA.

Transarticular elastic external skeletal fixator correction of a stifle rotational deformity and patellar luxation in a dog.

OBJECTIVE: To report the preoperative evaluation, treatment with transarticular elastic external skeletal fixation (ESF), and outcome of a dog with bilateral medial patellar luxation (MPL) and stifle rotational deformity. ANIMAL: One nonambulatory, 2.5-month-old, 7.5-kg mixed-breed intact female dog. STUDY DESIGN: Case report METHODS: Complex pelvic limb deformities were assessed with physical examination and computed tomography (CT) and characterized as bilateral grade 4 MPL and 90° internal rotation of the tibia in relation to the femur. Three-dimensional imaging and bone models were used to quantify the deformity and rehearse surgical correction. Transarticular elastic chains between ESF pins in the femur and tibia were used to gradually correct stifle rotational malalignment on each pelvic limb. Soft tissue releases, imbrication, and a transphyseal staple were used to correct the patellar luxation (PL) and femoral varus. The dog was reevaluated for 1 year postoperatively. RESULTS: Short- and long-term management included intensive physical rehabilitation to increase pelvic limb strength and function. Surgical treatment resulted in resolution of the PL and neutral stifle alignment. The dog was able to ambulate with persistent decreased range of motion of the stifle. CONCLUSION: Transarticular elastic chains and femoral physeal stapling improved the function of a dog with severe bone deformities and PL in a growing dog.

Computed Tomographic Measurement of Trochlear Depth in Three Breeds of Brachycephalic Dog.

OBJECTIVE: The aim of this study was to determine the trochlear sulcus depth of three common brachycephalic breeds at risk of medial patellar luxation. STUDY DESIGN: Retrospective blinded clinical study using a previously validated ratio (T/P) of maximal trochlear sulcus depth (T) and maximal patellar craniocaudal thickness (P) measured on computed tomography, to assess trochlear sulcus depth in Pugs, French Bulldogs and English Bulldogs without clinical patellar luxation. The effect of breed on T/P was assessed using one-way linear regression models. RESULTS: The mean T/P was affected by breed (p < 0.001). There was significant difference between Pugs (0.45) and French Bulldogs (0.38) and between Pugs and English Bulldogs (0.4). There was no significant difference between Pugs and previously published data for non-brachycephalic and mixed breed dogs (0.46) (p = 0.39). Mean T/P was significantly reduced in the brachycephalic dog breeds combined compared with the previously published data (p < 0.001). CONCLUSION: The trochlear sulcus varies by breed and was more shallow in French and English Bulldogs than Pugs, hence a shallow sulcus may be a breed-driven characteristic. The three breeds assessed are at risk of patellar luxation but sulcus depth did not directly correlate with previously published risk factors-the contribution of sulcus depth to the aetiopathogenesis of patellar luxation remains unclear. Trochlear recession to achieve patellar coverage of 50% may be excessive considering maximal breed normal depth.

Role of Lipocalin-Type Prostaglandin D Synthase in Experimental Osteoarthritis.

OBJECTIVE: Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the formation of prostaglandin D2 (PGD2 ), which has important roles in inflammation and cartilage metabolism. We undertook this study to investigate the role of L-PGDS in the pathogenesis of osteoarthritis (OA) using an experimental mouse model. METHODS: Experimental OA was induced in wild-type (WT) and L-PGDS-deficient (L-PGDS-/- ) mice (n = 10 per genotype) by destabilization of the medial meniscus (DMM). Cartilage degradation was evaluated by histology. The expression of matrix metalloproteinase 13 (MMP-13) and ADAMTS-5 was assessed by immunohistochemistry. Bone changes were determined by micro-computed tomography. Cartilage explants from L-PGDS-/- and WT mice (n = 6 per genotype) were treated with interleukin-1α (IL-1α) ex vivo in order to evaluate proteoglycan degradation. Moreover, the effect of intraarticular injection of a recombinant adeno-associated virus type 2/5 (rAAV2/5) encoding L-PGDS on OA progression was evaluated in WT mice (n = 9 per group). RESULTS: Compared to WT mice, L-PGDS-/- mice had exacerbated cartilage degradation and enhanced expression of MMP-13 and ADAMTS-5 (P < 0.05). Furthermore, L-PGDS-/- mice displayed increased synovitis and subchondral bone changes (P < 0.05). Cartilage explants from L-PGDS-/- mice showed enhanced proteoglycan degradation following treatment with IL-1α (P < 0.05). Intraarticular injection of rAAV2/5 encoding L-PGDS attenuated the severity of DMM-induced OA-like changes in WT mice (P < 0.05). The L-PGDS level was increased in OA tissues of WT mice (P < 0.05). CONCLUSION: Collectively, these findings suggest a protective role of L-PGDS in OA, and therefore enhancing levels of L-PGDS may constitute a promising therapeutic strategy.

Effectiveness of Led Photobiomodulation Therapy on Treatment With Knee Osteoarthritis: A Rat Study.

OBJECTIVE: The present study aimed to evaluate the effectiveness of photobiomodulation therapy by light-emitting diode on osteoarthritis treatment in the knees of rats. DESIGN: Twenty male Wistar rats were randomly assigned into two experimental groups: OAC: animals subjected to induction of osteoarthritis, without therapeutic intervention and the group OAL: animals subjected to induction of osteoarthritis treated with light-emitting diode photobiomodulation therapy (850 nm, 200 mW, 6 J). RESULTS: The results of gait analysis showed no statistical difference between the groups. The histological findings showed that the OAL group presented abnormal chondrocyte orientation, yet with less irregularities along fibrillation and the joint tissue. Thus, it presented a lower degenerative process when evaluated by the Osteoarthritis Research Society International. Likewise, in the immunohistochemical analysis, the OAL group showed higher collagen 2 and transforming growth factor ß immunoexpression when compared with the OAC group. CONCLUSIONS: Given the above, it is possible to suggest that the photobiomodulation therapy by light-emitting diode had positive effects on the expression of extracellular matrix proteins responsible for synthesis of articular tissue.