Comparison of the effects of caudal pole hemi-meniscectomy and complete medial meniscectomy in the canine stifle joint

OBJECTIVE: To compare the effects of caudal pole hemi-meniscectomy (CPHM) and complete medial meniscectomy (MM), specifically with respect to development of secondary osteoarthritis, in the stifle joints of clinically normal dogs. ANIMALS: 14 large-breed dogs. PROCEDURE: Unilateral CPHM (7 dogs) or MM (7) was performed, and the left stifle joints served as untreated control joints. Gait was assessed in all dogs before surgery and at 4, 8, 12, and 16 weeks postoperatively. After euthanasia, joints were evaluated grossly; Mankin cartilage scores, subchondral bone density assessment, and articular cartilage proteoglycan extraction and western blot analyses of 3B3(-) and 7D4 epitopes were performed. RESULTS: Weight distribution on control limbs exceeded that of treated limbs at 4 and 16 weeks after surgery in the CPHM group and at 4 and 8 weeks after surgery in the MM group; weight distribution was not significantly different between the 2 groups. After 16 weeks, incomplete meniscal regeneration and cartilage fibrillation on the medial aspect of the tibial plateau and medial femoral condyle were detected in treated joints in both groups. Mankin cartilage scores, subchondral bone density, and immunoexpression of 3B3(-) or 7D4 in articular cartilage in CPHM- or MM-treated joints were similar; 7D4 epitope concentration in synovial fluid was significantly greater in the MM-treated joints than in CPHM-treated joints. CONCLUSIONS AND CLINICAL RELEVANCE: Overall severity of secondary osteoarthritis induced by CPHM and MM was similar. Investigation of 7D4 epitope concentration in synovial fluid suggested that CPHM was associated with less disruption of chondrocyte metabolism.     

Evaluation of avocado and soybean unsaponifiable extracts for treatment of horses with experimentally induced osteoarthritis

OBJECTIVE: To evaluate the use of a combination of avocado and soybean unsaponifiable (ASU) extracts for the treatment of experimentally induced osteoarthritis in horses. ANIMALS: 16 horses. PROCEDURES: Osteoarthritis was induced via osteochondral fragmentation in 1 middle carpal joint of each horse; the other joint underwent a sham operation. Horses were randomly allocated to receive oral treatment with ASU extracts (1:2 [avocado-to-soybean] ratio mixed in 6 mL of molasses; n = 8) or molasses (6 mL) alone (placebo treatment; 8) once daily from days 0 to 70. Lameness, response to joint flexion, synovial effusion, gross and histologic joint assessments, and serum and synovial fluid biochemical data were compared between treatment groups to identify effects of treatment. RESULTS: Osteochondral fragmentation induced significant increases in various variables indicative of joint pain and disease. Treatment with ASU extracts did not have an effect on signs of pain or lameness; however, there was a significant reduction in severity of articular cartilage erosion and synovial hemorrhage (assessed grossly) and significant increase in articular cartilage glycosaminoglycan synthesis, compared with placebo-treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Although treatment with ASU extracts did not decrease clinical signs of pain in horses with experimentally induced osteoarthritis, there did appear to be a disease-modifying effect of treatment, compared with findings in placebo-treated horses. These objective data support the use of ASU extracts as a disease-modifying treatment for management of osteoarthritis in horses.     

Metalloproteinases and tumor necrosis factor-alpha activities in synovial fluids of horses: correlation with articular cartilage alterations

Early detection of osteoarthritis in horses represents a challenge for equine practitioners. Several biological markers have been implicated in the pathological processes involved in articular cartilage destruction. To further document cartilage matrix proteases production, synovial fluid was collected from 14 horses (90 joints) before they were subjected to euthanasia. Growth macroscopic examination of the joints gave information on cartilage alterations. Samples were analyzed for matrix metalloproteinase (MMPs) activities by gelatin zymography and tumor necrosis factor alpha (TNF-alpha) cytotoxicity using L929 cells. Significant increase of MMP-9 monomer and dimer were found in synovial fluids of joints with severe cartilage alterations. On the contrary, the activity of TNF-alpha was not correlated to the degree of joint damage. The levels of MMP-9 monomer and dimer in the synovial fluid could reflect cartilage alteration in arthritis in the horse.     

In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fluid compartments and articular cartilage in an osteochondrial defect model

The uptake and distribution of intramuscularly (IM) administered tritium-labeled polysulfated glycosaminoglycan (³H-PSGAG) in serum, synovial fluid, and articular cartilage of eight horses was quantitated, and hyaluronic acid (HA) concentration of the middle carpal joint was evaluated in a pharmacokinetic study. A full-thickness articular cartilage defect, created on the distal articular surface of the left radial carpal bone of each horse served as an osteochondral defect model. ³H-PSGAG (500 mg) was injected IM, between 14 and 35 days after creation of the defects. Scintillation analysis of serum and synovial fluid, collected from both middle carpal joints at specific predetermined times up to 96 hours post-injection, revealed mean ³H-PSGAG concentrations peaked at 2 hours post-injection. ³H-PSGAG was detected in cartilage and subchondral bone 96 hours post-injection in samples from all eight horses. There were no statistically significant differences in ³H-PSGAG concentration of synovial fluid or cartilage between cartilage defect and control (right middle carpal) joints.

HA assay of synovial fluid revealed concentrations significantly increased at 24, 48, and 96 hours post-injection in both joints. The concentration nearly doubled 48 hours post-injection. However, no statistically significant differences were found between synovial concentrations of HA in cartilage defect and control joints.

³H-PSGAG administered IM to horses, was distributed in the blood, synovial fluid, and articular cartilage. HA concentrations in synovial fluid increased after IM administration of polysulfated glycosaminoglycan.     

Effects of continuous oral administration of phenylbutazone on biomarkers of cartilage and bone metabolism in horses

OBJECTIVE: To evaluate the effects of continuous oral administration of phenylbutazone on serum and synovial fluid biomarkers of skeletal matrix metabolism in horses. ANIMALS: 11 adult female horses without clinical or radiographic evidence of joint disease. PROCEDURES: Horses were randomly assigned to control or treatment groups. Phenylbutazone was administered orally twice daily at a dose of 4.4 mg/kg for 3 days to the treatment group and subsequently at a dose of 2.2 mg/kg for 7 days. Serum and radiocarpal synovial fluid samples were obtained at baseline and thereafter at regular intervals for 4 weeks. Biomarkers of cartilage aggrecan synthesis (chondroitin sulfate 846) and type II collagen synthesis (procollagen type II C-propeptide) and degradation (collagen type II cleavage) were assayed. Biomarkers of bone synthesis (osteocalcin) and resorption (C-terminal telopeptide of type I collagen) were also measured. RESULTS: No significant differences were found between control and treatment groups or temporally for the biomarkers chondroitin sulfate 846, procollagen type II C-propeptide, collagen type II cleavage, and C-terminal telopeptide of type I collagen in serum or synovial fluid. A significant increase in osteocalcin concentration occurred in synovial fluid during treatment in the treated group. No treatment effect was detected for serum osteocalcin concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that continuous phenylbutazone administration at recommended doses altered some biomarkers in healthy equine joints after short periods of administration. Increased osteocalcin concentration may indicate an undetermined anabolic effect of phenylbutazone administration on periarticular bone or transient induction of osteogenesis in articular chondrocytes or a mesenchymal subpopulation of synoviocytes.     

Povidone-iodine lavage treatment of experimentally induced equine infectious arthritis

Both tarsocrural joints of 4 horses were inoculated with 1.5 X 10(5) colony-forming units of Staphylococcus aureus. On days 1, 3, and 6, each horse had one tarsocrural joint lavaged with a balanced electrolyte solution and had the contralateral tarsocrural joint lavaged with 0.1% povidone-iodine solution. All horses were orally administered trimethoprim (5 mg/kg)/sufadiazine (25 mg/kg) combination twice daily and phenylbutazone (2 g) once daily for the duration of the study (21 days). On days 0, 1, 3, 6, 9, 14, and 21, synovial fluid specimens were collected and analyzed for color, clarity, total protein concentration, WBC count and differential, and mucin clot-forming ability. Synovial fluid specimens collected on days 1, 3, 6, 9, 14, and 21 were bacteriologically cultured. On day 21, all horses were euthanatized, the tarsocrural joints were opened and examined, synovial membrane specimens were collected, bacteriologically cultured, and histologically evaluated, and articular cartilage specimens were histochemically evaluated. Repeated measures analysis of variance were used to evaluate differences between lavage solutions and among days for objective measurements. A paired t test was used to evaluate differences between solutions for the indices of synovial membrane inflammation and articular cartilage staining intensity with safranin-O-fast green. To be considered significant, the probability of a type-I error was less than 0.05. Significant differences were not found between joints lavaged with electrolyte solution vs povidone-iodine solution for synovial total protein concentration, WBC count, results of synovial fluid and membrane bacteriologic culture, synovial membrane inflammation, or articular cartilage glycosaminoglycan concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

补肾活血方对骨性关节炎模型SD大鼠基质金属蛋白酶-1及前列腺素E2的影响

本试验旨在观察补肾活血方对骨性关节炎模型SD大鼠关节软骨中基质金属蛋白酶-1（MMP-1）和关节液中前列腺素E₂（PGE₂）水平的影响,以探讨补肾活血方对骨性关节炎关节软骨的保护机制。将24只SPF级健康雌性SD大鼠随机分为假手术组、西药组和中药组,通过切除两侧卵巢并切断右侧膝交叉及内侧副韧带建立骨性关节炎动物模型。术后第4周开始,中药组灌服补肾活血中药,西药组灌服等量的西乐葆,假手术组灌服等量的生理盐水,于术后第8周处死动物,采用骨性关节炎软骨病理变化评价系统（OARSI）评价关节软骨的病变,采用光镜观察软骨细胞生长情况,运用免疫组化法测定关节软骨中MMP-1的含量,抽取关节液做PGE₂测定,对比各组数据。结果显示,假手术组、西药组、中药组软骨退变程度依次减轻,光镜下,假手术组、西药组仅见少量软骨细胞,而中药组见大量软骨细胞增生;西药组中各层软骨细胞几乎都可见大量的MMP-1阳性表达,中药组和假手术组MMP-1阳性表达极显著低于西药组（P＜0.01）;中药组和假手术组关节液中的PGE₂分别显著和极显著低于西药组（P＜0.05,P＜0.01）;中药组和西药组分别较其术后4周的结果极显著升高（P＜0.01）。补肾活血方能显著抑制骨性关节炎关节软骨中MMP-1的表达及降低关节液中的PGE₂水平,促进软骨细胞生长,以减缓骨性关节炎的发展,故具有治疗骨性关节炎的潜力。     

Assessment of the effects of age and joint disease on hydroxyproline and glycosaminoglycan concentrations in synovial fluid from the metacarpophalangeal joint of horses

OBJECTIVE: To assess the effects of age and joint disease on hydroxyproline and glycosaminoglycan (GAG) concentrations in synovial fluid from the metacarpophalangeal joint of horses and evaluate the association of those concentrations with severity of osteoarthritis and general matrix metalloproteinase (MMP) activity. SAMPLE POPULATION: Synovial fluid was collected from the metacarpophalangeal joints of foals at birth (n = 10), 5-month-old foals (10), 11-month-old foals (5), and adult horses (73). PROCEDURE: Hydroxyproline and GAG concentrations were determined in synovial fluid samples. The severity of osteoarthritis in adult joints was quantified by use of a cartilage degeneration index (CDI) and assessment of general MMP-activity via a fluorogenic assay. RESULTS: Hydroxyproline and GAG concentrations in synovial fluid were highest in neonates and decreased with age. Concentrations reached a plateau in adults by 4 years and remained constant in healthy joints. In synovial fluid from osteoarthritic joints, hydroxyproline and GAG concentrations were not increased, compared with unaffected joints, but hydroxyproline were significantly correlated with the CDI and general MMP activity. There was no significant correlation between GAG concentration and CDI value or MMP activity. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in hydroxyproline concentration in synovial fluid appeared to indicate damage to collagen of the articular cartilage. In joints with osteoarthritis, the lack of high GAG concentration in synovial fluid and the absence of a significant correlation between GAG concentration and CDI values or MMP activity may severely limit the usefulness of this marker for monitoring equine joint disease.     

Glycosaminoglycans in horses with osteoarthritis

Horse articular cartilage glycosaminoglycans (GAGs) were measured in synovial fluids from 48 joints affected with osteoarthritis (OA), 22 normal joints, four joints with osteochondritis, three joints with traumatic arthritis and seven joints infected with bacteria. Serum and urine from individual horses were also examined for the presence of GAGs. High levels of GAGs were found in synovial fluids (SF) from horses with OA. In each case, the level was higher in the synovial fluid than in the serum or urine from the same horse. Horses with OA showed high GAG levels in SF, serum and urine compared to horses with normal and infected joints. High levels were also found in horses with osteochondritis and traumatic arthritis. Levels of synovial fluid GAG reflect cartilage destruction in arthritis and may be useful for monitoring disease progression in the equine species.     

Products resulting from cleavage of the interglobular domain of aggrecan in samples of synovial fluid collected from dogs with early- and late-stage osteoarthritis

OBJECTIVE: To investigate interglobular domain (IGD) cleavage of aggrecan in dogs with naturally developing osteoarthritis (OA). SAMPLE POPULATION: Samples of synovial fluid (SF) obtained from 3 cubital (elbow) joints and 3 stifle joints of 4 clinically normal dogs, 24 elbow joints of 12 dogs with early-stage OA, 8 stifle joints of 5 dogs with early-stage OA, and 10 stifle joints of 9 dogs with late-stage OA. PROCEDURE: Fractions of SF were assayed for total glycosaminoglycan (GAG) content and also subjected to Western blot analysis by use of monoclonal antibodies against neoepitopes generated by cleavage of the IGD of the aggrecan protein core by matrix metalloproteinase (MMP; BC-14) and aggrecanase (BC-3). RESULTS: Total GAG content of SF from joints of clinically normal dogs did not differ from that of dogs with early-stage OA. The GAG content of SF from joints of dogs with late-stage OA was significantly lower, compared with GAG content for other SF samples. Aggrecanase-generated fragments were detected in SF from all groups but not in all samples. Matrix metalloproteinase-generated fragments were not detected in any SF samples. In early-stage OA, high-molecular-weight aggrecanase-generated aggrecan catabolites were evident. CONCLUSIONS AND CLINICAL RELEVANCE: GAG content of SF obtained from dogs with late-stage OA is significantly decreased, suggesting proteoglycan depletion of cartilage. Aggrecanases, but not MMPs, are the major proteolytic enzymes responsible for IGD cleavage of aggrecan in canine joints. Analyses of SF samples to detect aggrecanase-generated catabolites may provide an early biomarker for discriminating early- and late-stage OA in dogs.     

Concentrations of chondroitin sulfate epitopes 3B3 and 7D4 in synovial fluid after intra-articular and extracapsular reconstruction of the cranial cruciate ligament in dogs

OBJECTIVE: To evaluate effects of intra-articular and extracapsular reconstruction of the cranial cruciate ligament (CCL) on metabolism of articular cartilage as reflected by concentrations of chondroitin sulfate epitopes 3B3 and 7D4 in synovial fluid. ANIMALS: 13 adult dogs. PROCEDURE: Each dog underwent unilateral CCL transection (CCLT). One month after CCLT, sham CCL reconstruction (3 dogs), intra-articular CCL reconstruction (5), or extracapsular CCL reconstruction (5) was performed. Synovial fluid was collected by direct arthrocentesis from CCLT and contralateral stifle joints immediately before (time 0) and 1, 3, and 5 months after CCLT. Fluid was examined for concentrations of 3B3 and 7D4 epitopes and total sulfated glycosaminoglycan (GAG) content. RESULTS: Concentrations of 3B3, 7D4, and GAG, 3B3:GAG, or 7D4:GAG in CCLT joints did not differ significantly among treatment groups nor in the ratios of these variables in CCLT joints to contralateral joints at 3 months. In a longitudinal analysis, concentrations of 3B3 and 7D4, 3B3:GAG, and 7D4:GAG in CCLT joints in all groups changed significantly with time, but we did not detect time X group interactions. CONCLUSIONS AND CLINICAL RELEVANCE: Transection of CCL resulted in significant perturbation in articular cartilage metabolism as reflected by alterations in concentrations of 3B3 and 7D4 in synovial fluid. These changes over time were not significantly influenced by method of CCL reconstruction. We did not find evidence that surgical stabilization of CCL-deficient joints by intra-articular or extracapsular techniques had any effect on preventing alterations in composition of synovial fluid that have been associated with secondary osteoarthritis.     

Gentamicin concentrations in synovial fluid obtained from the tarsocrural joints of horses after implantation of gentamicin-impregnated collagen sponges

OBJECTIVE: To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge. ANIMALS: 6 healthy adult mares. PROCEDURES: A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of a fluorescence polarization immunoassay. Synovial membrane and cartilage specimens were collected 120 hours after implantation and evaluated histologically. RESULTS: Median peak synovial fluid gentamicin concentration of 168.9 microg/mL (range, 115.6 to 332 microg/mL) was achieved 3 hours after implantation. Synovial fluid gentamicin concentrations were < 4 microg/mL by 48 hours. Major histologic differences were not observed in the synovial membrane between control joints and joints implanted with gentamicin-impregnated sponges. Safranin-O fast green stain was not reduced in cartilage specimens obtained from treated joints, compared with those from control joints. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation of a gentamicin-impregnated collagen sponge in the tarsocrural joint of horses resulted in rapid release of gentamicin, with peak concentrations > 20 times the minimum inhibitory concentration reported for common pathogens that infect horses. A rapid decrease in synovial fluid gentamicin concentrations was detected. The purified bovine type I collagen sponges did not elicit substantial inflammation in the synovial membrane or cause mechanical trauma to the articular cartilage.     

Concentration of collagen, aggrecan and cartilage oligomeric matrix protein (COMP) in synovial fluid from equine middle carpal joints

The aim of the present investigation was to study the metabolic activity of the third carpal bone and the release of COMP, aggrecan and collagen type II molecules in the synovial fluid as a result of injury. Cartilage oligomeric matrix protein (COMP), aggrecan and collagen type II or fragments of these molecules released to the synovial fluid and serum (COMP) were quantified in samples from 73 left equine middle carpal joints from 2 breeds with different activity profiles (52 Standardbred trotters [STB] and 21 Swedish Warmblood riding horses [SWH]) and different articular cartilage lesions. Synovial and serum samples were analysed using inhibition ELISA for COMP and aggrecan. An ELISA that combines features of both the competitive and capture ELISAs was used for collagen type II. COMP and aggrecan concentrations decreased in synovial fluid from the joints with moderate lesions of STB compared with the normal joints; COMP from 16.6 to 12.0 microg/ml and aggrecan from 93.0 to 68.1 microg/ml. In serum, COMP concentrations were also lowered in the STB with moderate lesions compared with the normal joints, while in the SWH, the COMP concentration in synovial fluids from joints with moderate lesions was somewhat increased at 19.6 microg/ml compared with the normal joints (17.6 microg/ml). The ratio between aggrecan/COMP in the synovial fluid from joints with moderate lesions was higher in the STB (6.2) than in the SWH (3.4). The level of collagen type II in synovial fluid was higher in the SWH (8.8 microg/ml) than the STB (1.6 microg/ml), but there was no correlation between joint damage and collagen concentrations in synovial fluids (10.0 and 1.8 microg/ml in joints with moderate lesions from SWH and STB, respectively). A marked difference in COMP synthesised upon metabolic labelling between the normal and osteoarthritic cartilage was seen and the synthesis of COMP in the articular cartilage of the third carpal bone with moderate articular lesions (from an STB) was lower than in the joint with mild lesions. This difference between breeds may reflect different load characters, in release of macromolecules in osteoarthritic and normal joints. This a novel finding that should be considered in studies of equine traumatic arthritis.     

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.     

A comparison of two techniques for arthrocentesis of the equine metacarpophalangeal joint

Because arthrocentesis of the metacarpophalangeal joint through the proximal palmar pouch may induce synovial haemorrhage, this study evaluated arthrocentesis through the lateral collateral sesamoidean ligament. The proximal palmar pouch and collateral sesamoidean ligament approaches were used in contralateral forelimbs to obtain paired initial synovial fluid samples from 16 horses 12 to 15 h before being killed. Synovial fluid samples also were collected from the same joints at necropsy and the subcutis, synovium and articular cartilage were evaluated. Metacarpophalangeal joint arthrocentesis through the collateral seamoidean ligament yielded fewer haemorrhagic synovial fluid samples with less subcutaneous and synovial inflammation, and also yielded 2 ml of synovial fluid more often than arthrocentesis through the proximal palmar pouch.     

Changes in Third Carpal Bone Articular Cartilage After Synovectomy in Normal and Inflamed Joints

Objective —To determine if arthroscopic synovectomy in normal and inflamed joints had temporal or site-related effects on articular cartilage.
Study Design —Alterations in equine third carpal bone articular cartilage were studied at two time periods: groups 1 and 2 (6 weeks) and groups 3 and 4 (2 weeks) after synovectomy in normal (groups 2 and 4) and inflamed carpi (groups 1 and 3).
Animal Population —16 carpi from eight horses.
Methods —Biochemical and biomechanical properties of dorsal and palmar articular cartilage were determined by radiolabeling, proteoglycan (PG) extraction, chromatography, electrophoresis, and indentation testing.
Results —Synovectomy in inflamed joints produced the greatest concentration of newly synthesized PG in articular cartilage by 2 weeks. Synovectomy in normal joints produced significantly greater newly synthesized PG in articular cartilage by 6 weeks. Endogenous PG was only significantly greater in inflamed joints after 6 weeks. Dorsal sites had greater newly synthesized and endogenous PG in some groups. Chromatographic profiles of newly synthesized PG demonstrated early and late PG peaks. Electrophoresis of late PG peak showed a toluidine blue-positive band that comigrated with human A1D1 PG monomer in the two groups with the most newly synthesized PG. This band was reactive with monoclonal antibody 1C6 specific for the hyaluronic acid-binding region of aggrecan. For the material properties evaluated, only Poisson's ratio was significantly decreased between groups as a function of time (6 weeks < 2 weeks), and this was most pronounced in the thicker dorsal sites.
Conclusions —Synovectomy in inflamed joints produced site-specific, significantly greater responses in articular cartilage as compared with synovectomy in normal joints.
Clinical Relevance —Synovectomy may not be beneficial to the articular cartilage in inflamed joints.     

Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis

OBJECTIVE: To assess the clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum (ACS) in the treatment of experimentally induced osteoarthritis in horses. ANIMALS: 16 horses. PROCEDURES: Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. In 8 placebo- and 8 ACS-treated horses, 6 mL of PBS solution or 6 mL of ACS was injected into the osteoarthritis-affected joint on days 14, 21, 28, and 35, respectively; PBS solution was administered in the other sham-operated joints. Evaluations included clinical assessment of lameness and synovial fluid analysis (performed biweekly); gross pathologic and histologic examinations of cartilage and synovial membrane samples were performed at necropsy. RESULTS: No adverse treatment-related events were detected. Horses that were treated with ACS had significant clinical improvement in lameness, unlike the placebo-treated horses. Among the osteoarthritis-affected joints, ACS treatment significantly decreased synovial membrane hyperplasia, compared with placebo-treated joints; although not significant, the ACS-treated joints also appeared to have less gross cartilage fibrillation and synovial membrane hemorrhage. The synovial fluid concentration of interleukin-1 receptor antagonist (assessed by use of mouse anti-interleukin-1 receptor antagonist antibody) was increased following treatment with ACS. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this controlled study indicated that there was significant clinical and histologic improvement in osteoarthritis-affected joints of horses following treatment with ACS, compared with placebo treatment. On the basis of these findings, further controlled clinical trials to assess this treatment are warranted, and investigation of the mechanisms of action of ACS should be pursued concurrently.     

Evaluation of a Collagenase Generated Osteoarthritis Biomarker in the Synovial Fluid from Elbow Joints of Dogs with Medial Coronoid Disease and Unaffected Dogs

Objective— To evaluate whether synovial fluid concentrations of an osteoarthritis biomarker in dysplastic canine elbows with medial coronoid disease (MCD) are elevated compared with unaffected elbows and to determine if these concentrations correlate to the degree of articular cartilage damage.
Study Design— Cross sectional clinical study.
Animals— Dogs (n=19; 35 elbows) with MCD and dogs (8; 16 elbows) with unaffected elbows.
Methods— Concentrations of a collagenase-generated cleavage neoepitope of type II collagen (Col2-3/4C_{long mono}, or C2C) in joint fluid from elbows were analyzed and compared between dogs with MCD and unaffected dogs. Correlation of C2C concentration with subjective grading of articular cartilage surface damage was also evaluated.
Results— Mean (±SD) C2C concentration from MCD dogs was significantly higher (112.3±24.8 ng/mL) than in unaffected dogs (76.1±16.9 ng/mL; P <.05). There was a moderate correlation between cartilage damage grade and increasing C2C concentrations ( P <.05, r=0.62)
Conclusion— C2C concentrations are elevated in the synovial fluid of dogs with MCD compared with unaffected elbows, and a moderate, significant correlation was identified between these concentrations and subjective grading of articular cartilage damage.
Clinical Relevance— This preliminary data suggest that C2C concentrations in synovial fluid may have potential as a biomarker for diagnosis of articular cartilage damage associated with MCD and as a means of objectively determining the degree of articular cartilage damage.