Lymphocyte populations in joint tissues from dogs with inflammatory stifle arthritis and associated degenerative cranial cruciate ligament rupture.

OBJECTIVE: To evaluate lymphocyte populations in stifle synovium and synovial fluid of dogs with degenerative cranial cruciate ligament rupture (CCLR). STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (n=25) with stifle arthritis and CCLR, 7 dogs with arthritis associated with cartilage degeneration (osteoarthritis [OA]), and 12 healthy Beagle dogs with intact CCL. METHODS: Arthritis was graded radiographically in CCLR dogs. After collection of joint tissues, mononuclear cells were isolated and subsequently analyzed using flow cytometry for expression of CD3, CD4, CD8, and CD21. RESULTS: The proportions of CD4(+) T helper lymphocytes, CD8(+) cytotoxic T lymphocytes, and CD3(+) CD4(-) CD8(-) T lymphocytes were increased in synovium from dogs with CCLR compared with synovium from healthy Beagle dogs (P<.05). The proportion of CD3(+) CD4(-) CD8(-) T lymphocytes in synovial fluid was increased in dogs with CCLR compared with dogs with OA (P<.05). In dogs with CCLR, the proportion of CD3(+) CD4(-) CD8(-) T lymphocytes in synovial fluid was inversely correlated with radiographic arthritis (S(R) =-0.68, P<.005). CONCLUSION: Lymphocytic inflammation of stifle synovium and synovial fluid is an important feature of the CCLR arthropathy. Lymphocyte populations include T lymphocytes expressing CD4 and CD8, and CD3(+) CD4(-) CD8(-) T lymphocytes. Presence of CD3(+) CD4(-) CD8(-) T lymphocytes was associated with development of stifle synovitis. Further work is needed to fully identify the phenotype of these cells.

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 (r(2) = 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.

Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis?

It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR (n=51) and healthy dogs with normal stifles (n=9). Arthritis was assessed radiographically in CCLR dogs. Bacterial load was assessed using qPCR and broad-ranging 16S rRNA primers. qRT-PCR was used to estimate expression of the T lymphocyte antigen receptor (TCR Vß), CD3ɛ, tartrate-resistant acid phosphatase (TRAP), IL-4, IL-17, and TNF-α genes. Severity of synovitis was assessed histologically. Bacterial load was increased in arthritic stifles, when compared with healthy stifles. Histologic synovitis in arthritic stifles was mononuclear and was significantly correlated with bacterial load (1 of 2 primer sets) (S(R)=0.49, p<0.001). In arthritic stifles, expression of TRAP in synovium was increased relative to healthy stifles. Expression of pro-inflammatory genes was not correlated with bacterial load, histologic inflammation, or radiographic arthritis. Translocation of bacterial material to the canine stifle is related to the presence of joint inflammation. The lack of a strong positive correlation suggests that bacterial load is unlikely to be a primary pro-inflammatory factor. However, dysregulation of immune responses within synovial tissues may be dependent upon an environmental microbial trigger.

Seasonal variation in detection of bacterial DNA in arthritic stifle joints of dogs with cranial cruciate ligament rupture using PCR amplification of the 16S rRNA gene.

An underappreciated cause and effect relationship between environmental bacteria and arthritis may exist. Previously, we found that stifle arthritis in dogs was associated with the presence of environmental bacteria within synovium. Cranial cruciate ligament rupture (CCLR) is often associated with stifle arthritis in dogs. We now wished to determine whether seasonal variation in detection of bacterial material may exist in affected dogs, and to also conduct analyses of both synovium and synovial fluid. We also wished to analyze a larger clone library of the 16S rRNA gene to further understanding of the microbial population in the canine stifle. Synovial biopsies were obtained from 117 affected dogs from January to December 2006. Using PCR, synovium and synovial fluid were tested for Borrelia burgdorferi and Stenotrophomonas maltophilia DNA. Broad-ranging 16S rRNA primers were also used and PCR products were cloned and sequenced for bacterial identification. Overall, 41% of arthritic canine stifle joints contained bacterial DNA. Detection of bacterial DNA in synovial fluid samples was increased, when compared with synovium (p<0.01). Detection rates were highest in the winter and spring and lowest in the summer period, suggesting environmental factors influence the risk of translocation to the stifle. Organisms detected were predominately Gram's negative Proteobacteria, particularly the orders Rhizobiales (32.8% of clones) and Burkholderiales (20.0% of clones), usually as part of a polymicrobial population. PCR-positivity was inversely correlated with severity of arthritis assessed radiographically and with dog age. Bacterial translocation to the canine stifle may be associated with changes to the indoor environment.

Risk factors associated with fibular fracture after tibial plateau leveling osteotomy.

OBJECTIVE: To determine the incidence of, and risk factors for, fibular fracture after tibial plateau leveling osteotomy (TPLO) in dogs. STUDY DESIGN: Case series. SAMPLE POPULATION: TPLO (n=168) on 142 dogs. METHODS: Medical records (January 2006-September 2007) and radiographs of all dogs that had TPLO were reviewed. Data retrieved were breed, sex, age, weight, type of plate, use of a jig, time to recheck, preoperative tibial plateau angle (TPA), immediate postoperative TPA, and presence or absence of fibular fracture. RESULTS: Fibular fractures occurred in 5.4% TPLOs. Body weight, change in TPA, and preoperative TPA were significantly higher in dogs with fibular fracture. TPLO without use of a jig was significantly associated with fibular fracture. Age, postoperative TPA, and plate type were not significantly associated with fibular fracture. CONCLUSIONS: Fibular fracture is uncommon after TPLO. Risk factors are increased body weight, greater preoperative TPA, greater change in TPA, and TPLO performed without a jig. All fractures occurred during convalescence. CLINICAL RELEVANCE: Owners should be warned of potential complications and risk factors associated for fibular fracture after TPLO.

Clinical application of recombinant human bone morphogenetic protein-2 in 4 dogs.

OBJECTIVE: To describe outcome in dogs with insufficient bone healing treated with recombinant human bone morphogenetic protein-2 (rhBMP-2). STUDY DESIGN: Retrospective study. ANIMALS: Four dogs clinically affected with delayed union or nonunion bone healing. METHODS: Medical records were reviewed for signalment, clinical problem, treatment, and outcome. RESULTS: Four dogs that had delayed- or nonunion of bone fracture, osteotomy, or arthrodesis were treated with either minimally invasive, fluoroscopically guided, percutaneous administration or direct surgical application of rhBMP-2. Doses used ranged from 0.2 to 1.6 mg of rhBMP-2. In 3 dogs, a calcium phosphate matrix (CPM) carrier was used whereas in 1 dog commercially prepared rhBMP-2 impregnated in an absorbable collagen sponge (INFUSE Bone Graft) was used. This latter dog had osteomyelitis associated with implant infection before rhBMP-2 administration. Rapid radiographic union was noted in all dogs with excellent long-term outcome. Adverse effects were minimal and included transient worsening of lameness after percutaneous administration of rhBMP-2 in 2 dogs. CONCLUSIONS: rhBMP-2 stimulated rapid bone formation at delayed- or nonunion sites resulting in radiographic bone union with minimal adverse effects and excellent long-term outcome in 4 dogs. CLINICAL RELEVANCE: Direct intraoperative administration or fluoroscopically guided, minimally invasive delivery of rhBMP-2 may be an effective treatment modality for bone delayed- or nonunions and could potentially be used to stimulate new bone production in a variety of orthopedic surgical conditions in dogs.

Detection of DNA from a range of bacterial species in the knee joints of dogs with inflammatory knee arthritis and associated degenerative anterior cruciate ligament rupture.

Mixtures of bacterial nucleic acids can often be detected in synovial joints affected with arthritis. We investigated the potential role of such mixtures of bacterial nucleic acids in the pathogenesis of arthritis in a naturally occurring canine model. Dogs with a common inflammatory knee arthritis in which associated pathological degenerative anterior cruciate ligament (ACL) rupture often develops were studied. Synovial biopsies were obtained from 43 dogs with the naturally occurring ACL rupture arthropathy, 12 dogs with normal knees and intact ACL, and 16 dogs with normal knees and experimentally induced ACL rupture. Using PCR, specimens were tested for Borrelia burgdorferi OspA and p66 gene sequences. Broad-ranging 16S rRNA primers were also used; 'panbacterial' PCR products were cloned and multiple clones were sequenced for bacterial identification. Synovium was also studied histologically. The presence of bacterial DNA within the synovium was significantly associated with the naturally occurring ACL rupture arthropathy (p<0.05); knee joints from 37% of these dogs were PCR-positive. Mixtures of bacterial DNA were common and often included environmental bacteria; predominant organisms included Borrelia burgdorferi and Stenotrophomonas maltophilia. DNA from environmental bacteria was only found in dogs with the naturally occurring ACL rupture arthopathy; joints from 33% of affected dogs contained such bacterial DNA. Synovial inflammation developed in dogs with both naturally occurring and experimentally induced ACL rupture, when compared with intact ACL controls (p<0.01). These results indicate that mixtures of DNA derived from environmental bacteria are commonly found in the knee joint of a naturally occurring canine arthropathy, often in association with a recognized joint pathogen. Our results also suggest that knee instability alone is not responsible for this finding and have led us to hypothesize that mixtures of bacterial DNA are an important causative factor in the pathogenesis of inflammatory arthritis in this canine model.

Long-term outcome of juvenile pubic symphysiodesis and triple pelvic osteotomy in dogs with hip dysplasia.

OBJECTIVE: To compare long-term outcomes of juvenile pubic symphysiodesis (JPS) and triple pelvic osteotomy (TPO) in dogs with hip dysplasia. DESIGN: Prospective clinical trial. ANIMALS: 18 dogs with hip dysplasia (ie, distraction index > or = 0.5 in at least 1 hip joint and no, mild, or moderate radiographic evidence of degenerative joint disease [DJD]). PROCEDURES: Dogs between 4 and 5.5 months old at enrollment were assigned to undergo JPS, and dogs between 5 and 12 months old were assigned to undergo TPO. All dogs were reexamined at 2 years of age. RESULTS: At 2 years of age, there were no significant differences between groups in regard to lameness scores, angle of extension of the hip joints, distraction index, peak vertical force, acetabular angle, radiographic DJD score, or owner-assigned scores of clinical function. Dorsal acetabular rim angle was significantly higher in dogs that underwent JPS than in dogs that underwent TPO. For dogs that underwent TPO, dorsal acetabular rim angle was significantly decreased and acetabular angle was significantly increased at 2 years of age, compared with values obtained prior to surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that JPS and TPO have similar effects on hip joint conformation in dogs with moderate to severe hip dysplasia but that neither procedure eliminates the hip joint laxity characteristic of hip dysplasia or the progression of degenerative changes.

Gluteal muscle attachment during proximal femoral reconstruction in a canine model.

In this 18 month in vivo canine study we compared three methods of attaching the gluteal muscles to the proximal femur during hip reconstruction with an allograft-prosthesis composite (APC). All three methods are commonly practiced in human hip revision surgery and data on their effectiveness in dogs is directly relevant to human treatment. The methods compared were host gluteal tendon sutured to allograft tendon, host greater trochanter apposed to allograft using a cable grip system, and host cortical bone shells around the allograft secured with cerclage wires. For each method, we assessed changes in allograft-host bone fusion, weight bearing, gluteal muscle mass, and structural properties through qualitative radiography, gait analysis, histology, and biomechanical testing. Hip reconstruction using the WRAP method resulted in the greatest limb use with complete resolution of gluteal muscle atrophy 18 months after surgery. This method yielded a stronger, more stable hip joint that allowed for more normal limb function. These hips had the more rapid rate of bony union at the host bone-allograft junction and little resorption of the graft. The increased limb use and resultant larger gluteal muscle mass conferred to the WRAP hip composites the greatest tensile strength and stiffness when tested 18 months after reconstruction. There was a large amount of new bone formation on the periosteal surface where the WRAP reconstructions had an overlay of live bone that resulted in a more rapid union and increased cortical width at the level of the osteotomy. New bone also penetrated into the allograft a greater distance from the osteotomy in the WRAP group.

COL-3 inhibition of collagen fragmentation in ruptured cranial cruciate ligament explants from dogs with stifle arthritis.

Inhibition of collagen fragment generation in canine cranial cruciate ligament (CCL) explant cultures by the matrix metalloprotease inhibitor (6-demethyl)-6-deoxy-4-dedimethylamino tetracycline (COL-3) was studied. Cranial cruciate ligament specimens were collected from dogs with inflammatory stifle arthritis/CCL rupture and dogs with normal stifles. Explant cultures from each CCL specimen included one COL-3 treated explant and a baseline control; explants from 12 ruptured CCLs were prepared in triplicate and a protease inhibitor cocktail positive control was used. Explant supernatants were analyzed for generation of collagen fragments after two days. Treatment of ruptured CCL explants with 10(-4)M COL-3 decreased generation of collagen fragments. The extent of this inhibition was increased in explants treated with a protease inhibitor cocktail. Generation of collagen fragments was increased in ruptured CCLs, when compared with intact CCLs. It is concluded that generation of collagen fragments was increased in pathological ruptured CCL explants. This degradation could be significantly inhibited in vitro by 10(-4)M COL-3.

Histomorphometric analysis of articular cartilage, zone of calcified cartilage, and subchondral bone plate in femoral heads from clinically normal dogs and dogs with moderate or severe osteoarthritis.

OBJECTIVE: To quantify and compare the microscopic changes in articular cartilage (AC), zone of calcified cartilage (ZCC), and subchondral bone plate in femoral heads from clinically normal dogs and dogs with moderate or severe osteoarthritis. SAMPLE POPULATION: Femoral heads from clinically normal dogs (n = 16) and dogs with moderate (24) or severe (14) osteoarthritis. PROCEDURES: Femoral heads were allocated to 3 categories (normal, moderate, or severe osteoarthritis) on the basis of radiographic findings, macroscopic findings, and histologic grade determined by use of a modified Mankin scale. Equally spaced 2-mm sections were cut in each femoral head in a coronal or transverse plane. Thickness of the AC, ZCC, and subchondral bone plate was recorded. RESULTS: Mean thickness of AC was significantly greater in samples with moderate and severe osteoarthritis than those considered normal. Mean thickness of the ZCC was significantly greater in samples with moderate and severe osteoarthritis than those considered normal. Mean thickness of the subchondral bone plate in samples with severe osteoarthritis was significantly greater than those with moderate osteoarthritis and those considered normal. A significant decrease in AC thickness was detected in the proximomedial area of femoral heads with severe osteoarthritis, compared with those considered normal. CONCLUSIONS AND CLINICAL RELEVANCE: A cause and effect association between thickening of subchondral structures and thinning and loss of the overlying AC was not detected. Changes in AC were associated with changes in the subchondral bone plate, which is compatible with the theory of adaptation in response to altered load distribution.

Histomorphometry of fragmented medial coronoid process in dogs: a comparison of affected and normal coronoid processes.

OBJECTIVE: To determine if fatigue microdamage is associated with fragmented medial coronoid process (FMCP). STUDY DESIGN: Prospective study. ANIMALS: Thirty-eight dogs were admitted for subtotal coronoid ostectomy as treatment for FMCP. Surgical specimens of medial coronoid process (MCP) were retrieved from treated dogs. Normal MCP were collected from 5 age- and breed-matched dogs and 2 age-matched research beagles that were euthanatized for reasons other than elbow disease. METHODS: MCP specimens from affected elbows were classified into 4 groups based on disease severity. Specimens were bulk-stained for microdamage using 1% basic fuchsin, embedded in polymethylmethacrylate and sectioned at 130 microm. Specimens were evaluated using epifluorescent microscopy (425-440 excitation, 475 nm barrier filter) for diffuse damage (D.DX), osteocyte loss, and porosity. Cartilage thickness was evaluated using bright field microscopy. Qualitative observations were also made. RESULTS: MCP specimens from affected elbows had increased D.Dx, increased osteocyte loss, and greater porosity than normal groups. Specimens classified as severe FMCP (Classes 3, 4) had the most fatigue microdamage. Some Class 1 specimens, defined as having no visible fissuring of the articular cartilage (AC), had large microcracks in trabecular bone. CONCLUSIONS: Accumulation of subchondral fatigue microdamage, is associated with MCP fragmentation. Fissuring occurs in the subchondral bone before gross fibrillation of articular cartilage develops. CLINICAL RELEVANCE: Accumulation of fatigue microdamage in the MCP is important in the pathogenesis of FMCP. The underlying cause of this microdamage accumulation must be identified before treatment plans that will prevent further osteoarthritis of the elbow joint can be designed.

Collagen fragmentation in ruptured canine cranial cruciate ligament explants.

Collagen fragmentation in cranial cruciate ligament (CCL) explants and stifle synovial fluid was investigated in dogs with ruptured and intact CCL. Cathepsin K and tartrate-resistant acid phosphatase (TRAP) activities were determined in CCL explant supernatants. Formation of collagen fragments was determined in explant supernatants and stifle synovial fluid. Cathepsin K(+) and TRAP(+) cells were stained specifically in histological sections of CCL. Formation of telopeptide collagen fragments was increased in ruptured CCL explants and stifle synovial fluid from dogs with ruptured CCL. In ruptured CCL explants, release of collagen fragments was associated with extracellular release of TRAP and the presence of cathepsin K(+) cells within CCL tissue. Cathepsin K(+) and TRAP(+) cells were only seen in ruptured CCL. It was concluded that infiltration of the CCL with TRAP(+) cells in dogs with CCL rupture is associated with increased collagenolysis. It is hypothesized that recruitment and activation of TRAP(+) mononuclear cells within the synovium and CCL precipitates CCL rupture through upregulation of collagenolytic enzymes and collagen degradation.

In vivo study on the short-term effect of radiofrequency energy on chondromalacic patellar cartilage and its correlation with calcified cartilage pathology in an equine model.

Chondromalacia can cause joint pain and synovial effusion with the potential for developing into osteoarthritis. Thermal chondroplasty using radiofrequency energy (RFE) has been reported to be superior to mechanical debridement for treating chondromalacia. We compared short-term changes in biomechanical properties of articular cartilage after treatment with monopolar (mRFE) or bipolar RFE (bRFE) or mechanical debridement (MD) on experimentally created grade II chondromalacia patellae. Chondromalacia patellae was created arthroscopically in both patellae of 15 ponies. Ten months after surgery, each patella was randomly assigned to one of four experimental groups: sham operated, untreated control; MD; bRFE; and mRFE. Animals were euthanized 6 months after treatment and fresh osteochondral sections were collected from the treated area, the border of the chondromalacic and nonchondromalacic area, and from two untreated areas for analysis of mechanical properties. The same areas were harvested from an additional six untreated ponies. The aggregate modulus (H(A)), Poisson's ratio (nu(s)), and permeability (k) were determined for each area under creep indentation, and cartilage thickness was measured with a needle probe. The relation between zone of calcified cartilage (ZCC) and mechanical properties of hyaline cartilage (HC) was assessed histomorphometrically. Treated areas of all four groups had inferior mechanical properties compared at the same location. The treated and border areas had significantly lower H(A) values than the untreated areas. Permeability values showed significant differences between bRFE and other treated groups. Chondromalacic areas showed thinning of cartilage compared to nonchondromalacic areas. Biomechanical properties of the injured cartilage were inferior to nonchondromalacic cartilage regardless of the treatment type. mRFE had the highest stiffness value compared to other treatments and significantly higher values than MD. A significant correlation was observed between the mechanical properties of HC and ZCC thickness.

Collagenolytic protease expression in cranial cruciate ligament and stifle synovial fluid in dogs with cranial cruciate ligament rupture.

OBJECTIVE: To determine expression of collagenolytic genes and collagen degradation in stifle tissues of dogs with ruptured cranial cruciate ligament (CCL). ANIMALS: Six dogs with CCL rupture and 11 dogs with intact CCL. PROCEDURES: Gene expression in CCL tissue and synovial fluid cells was studied using reverse transcriptase-polymerase chain reaction (RT-PCR). Collagen degradation was studied using CCL explant cultures and a synovial fluid bioassay. RESULTS: Expression of matrix metalloproteases (MMP) was not found in young Beagles with intact CCL; however, increased expression of MMP-3 was found in CCL tissue from older hounds with intact CCL, when compared with young Beagles. In dogs with ruptured CCL, expression of MMP-2 and -9 was increased in stifle tissues, when compared with dogs with intact CCL. Similar to MMP-9, expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin S was only found in stifle tissues from dogs with ruptured CCL; in contrast, expression of cathepsin K was found in all ruptured and intact CCL. Collagen degradation was increased in ruptured CCL, when compared with intact CCL. CONCLUSION: Rupture of the CCL is associated with up-regulation of expression of MMP-2 and -9 (gelatinase A and B), TRAP, and cathepsin S, and increased degradation of collagen. CLINICAL RELEVANCE: These findings suggest that MMP-2, -9, cathepsin S, and TRAP may be important mediators of progressive joint destruction in dogs with CCL rupture. These genes are markers for macrophages and dendritic cells. MMP and cathepsin S pathways may offer novel targets for anti-inflammatory medical therapy aimed at ameliorating joint degradation associated with inflammatory arthritis.

Localization of cathepsin K and tartrate-resistant acid phosphatase in synovium and cranial cruciate ligament in dogs with cruciate disease.

OBJECTIVE: To localize cathepsin K and tartrate-resistant acid phosphatase (TRAP) in synovium and cranial cruciate ligament (CCL) of dogs with cruciate disease. ANIMALS: Dogs (n=15) with cruciate disease and ruptured CCL, and 12 dogs with intact CCL. METHODS: Synovium and CCL were examined histologically and cells containing cathepsin K or TRAP were identified immunohistochemically and histochemically, respectively. RESULTS: Increased cellular localization of cathepsin K and TRAP was detected in synovium and ruptured CCL in dogs with cruciate disease, when compared with tissues from dogs with intact CCL. Inflammation of synovium with TRAP+ macrophage-like cells was seen in 73% of dogs with CCL disease, but was not seen in dogs with intact CCL. The presence of cathepsin K and TRAP protein in synovium and CCL tissues was significantly correlated in dogs with CCL rupture. CONCLUSION: Inflammation of the epiligament of ruptured CCL with cathepsin K+ and TRAP+ macrophage-like cells forms part of a similar, more generalized chronic inflammatory change within the periarticular tissues of the stifle of a large proportion of dogs with CCL rupture. CLINICAL RELEVANCE: Production of matrix-degrading enzymes by the synovium may induce progressive pathologic rupture of the CCL. Therefore, these collagenolytic pathways may offer a novel target for medical therapy of joint inflammation in canine patients with cruciate disease.

Progressive arthropathy in mice with a targeted disruption of the Mop3/Bmal-1 locus.

Disruption of the murine Mop3 (also known as Bmal1 or Arntl) locus results in a loss of behavioral and molecular circadian rhythms. Although Mop3 null mice do not display anomalies in early development, they do display reduced activity as they age. In an effort to explain this decreased activity, we characterized the physiological and anatomical changes that occurred with age. We observed that Mop3 null mice display an increased mortality after 26 weeks of age and a phenotype best described as a progressive noninflammatory arthropathy. Although little pathology is observed prior to 11 weeks of age, by 35 weeks of age essentially all Mop3 null animals develop joint ankylosis due to flowing ossification of ligaments and tendons and almost complete immobilization of weight-bearing and nonweight-bearing joints. This pathology appears to explain the decreased activity of Mop3 null mice and suggests that MOP3 is an inhibitor of ligament and tendon ossification.

Histomorphometric analysis of the proximal portion of the femur in dogs with moderate osteoarthritis.

OBJECTIVE: To describe the histomorphometric properties of epiphyseal and metaphyseal trabecular bone of the proximal portion of the femur of dogs with moderate osteoarthritis. SAMPLE POPULATION: Proximal portions of a femour from 24 dogs. PROCEDURE: The proximal portion of a femur was obtained from each dog. Eleven and thirteen specimens were sectioned in the transverse and coronal planes, respectively. Three evenly spaced sections from each specimen were chosen, surface stained, and digitized, and the stained areas were preferentially selected. Custom software was used for histomorphometric analysis of each section. A mixed-model analysis was used to evaluate the effect of slice location and region on 6 parameters, and a Fisher protected t test was used when differences were detected. RESULTS: There was a significant difference between the femoral head and femoral neck for all parameters tested. In coronal sections, the femoral neck was significantly more anisotropic than the femoral head. In transverse sections, the craniolateral region of the femoral neck was significantly more anisotropic than the caudomedial and craniomedial regions. CONCLUSIONS AND CLINICAL RELEVANCE: There is a predictable cancellous microarchitecture in the proximal portion of femurs from dogs with moderate osteoarthritis. Trabeculae are more numerous, thicker, and closer together but more randomly arranged in the femoral head than in the femoral neck. Dogs with moderate osteoarthritis had an increase in trabecular anisotropy in the craniolateral region of the femoral neck. However, there was no corresponding increase in trabecular alignment of the proximomedial region of the femoral head. Results support an association between trabecular alignment and the progression of osteoarthritis.

Cranial cruciate ligament pathophysiology in dogs with cruciate disease: a review.

Cruciate disease is a common cause of chronic lameness in dogs. Midsubstance rupture of the cranial cruciate ligament (CCL) arises from progressive pathological failure, often under conditions of normal loading in adult dogs with CCL instability. A high risk of rupture is associated with inflammation of the synovium and adaptive or degenerative changes in the cells and matrix of the CCL. In contrast, CCL rupture in puppies is usually associated with traumatic injury and avulsion of the CCL from its sites of attachment.

Femoral bone adaptation to stable long-term cemented total hip arthroplasty in dogs.

OBJECTIVE: To quantify long-term bone adaptation after stable cemented total hip arthroplasty (cTHA) in dogs. STUDY DESIGN: Clinical study. ANIMALS: Fourteen dogs. METHODS: Femoral specimens were collected from client-owned dogs that were donated after death because of causes unrelated to their cTHA. Mean (+/-SEM) dog age was 11.4+/-0.7 years and implant duration was 5.3+/-0.7 years. Implant stability was established from radiographic signs and gross mechanical stability. Femurs were evaluated at 3 levels based on implant length: proximal stem (PS), mid-stem (MS), and distal to stem (DS). Cortical area, medullary area, and porosity were measured at each level. Implanted femurs were compared to contralateral nonimplanted femurs. RESULTS: Cortical area and cortical porosity were significantly increased in implanted femurs compared to nonimplanted femurs. Cortical area was increased at the MS and DS levels, and porosity was increased at the PS and MS levels in implanted femurs. Porosity was greatest in the endosteal region at the PS and MS levels in implanted femurs. CONCLUSIONS: Significant differences in femoral geometry and cortical porosity were detected after long-term stable cTHA. Net bone loss proximally and increased bone mass distally support stress shielding as a important mechanical factor associated with bone adaptation. Distribution of porosity shifts to endosteal regions after long-term cTHA. CLINICAL RELEVANCE: Significant site-specific femoral adaptation occurs in response to stable cTHA and may precede implant loosening.