Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture.

Anterior cruciate ligament (ACL) rupture is an important condition of the human knee. Second ruptures are common and societal costs are substantial. Canine cranial cruciate ligament (CCL) rupture closely models the human disease.

Proinflammatory polarization of stifle synovial macrophages in dogs with cruciate ligament rupture.

Objective: To determine polarization of synovial macrophages during development of cruciate ligament rupture (CR) and determine whether differences in synovial macrophage polarization in CR, osteoarthritis (OA), and healthy joints exist.

Study Design: Prospective case-controlled study.

Animals: Client-owned dogs with unstable stifles with CR (n = 22), paired stable contralateral stifles with partial CR (pCR; n = 7), joints with OA not related to CR (n = 6), and clinically normal (Normal; n = 7) joints.

Multivariate genome-wide association analysis identifies novel and relevant variants associated with anterior cruciate ligament rupture risk in the dog model.

Background: Anterior cruciate ligament rupture (ACLR) is a debilitating and potentially life-changing condition in humans, as there is a high prevalence of early-onset osteoarthritis after injury. Identification of high-risk individuals before they become patients is important, as post-treatment lifetime burden of ACLR in the USA ranges from $7.6 to $17.

Use of a platelet-rich plasma-collagen scaffold as a bioenhanced repair treatment for management of partial cruciate ligament rupture in dogs.

Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period.

Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined.

Radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture.

Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging.

Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture.

Anterior cruciate ligament (ACL) rupture is a common condition that can be devastating and life changing, particularly in young adults. A non-contact mechanism is typical. Second ACL ruptures through rupture of the contralateral ACL or rupture of a graft repair is also common.

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common.

Role of calcitonin gene-related peptide in functional adaptation of the skeleton.

Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPα and CGRPβ. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton.

Computed tomographic imaging of subchondral fatigue cracks in the distal end of the third metacarpal bone in the thoroughbred racehorse can predict crack micromotion in an ex-vivo model.

Articular stress fracture arising from the distal end of the third metacarpal bone (MC3) is a common serious injury in Thoroughbred racehorses. Currently, there is no method for predicting fracture risk clinically. We describe an ex-vivo biomechanical model in which we measured subchondral crack micromotion under compressive loading that modeled high speed running.

Arthroscopic assessment of stifle synovitis in dogs with cranial cruciate ligament rupture.

Cranial cruciate ligament rupture (CR) is a degenerative condition in dogs that typically has a non-contact mechanism. Subsequent contralateral rupture often develops in dogs with unilateral CR. Synovitis severity is an important factor that promotes ligament degradation.

Functional adaptation in female rats: the role of estrogen signaling.

Background: Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERβ), a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER). GPER is distributed throughout the nervous system, but little is known about its effects on bone.

Contralateral cruciate survival in dogs with unilateral non-contact cranial cruciate ligament rupture.

Background: Non-contact cranial cruciate ligament rupture (CrCLR) is an important cause of lameness in client-owned dogs and typically occurs without obvious injury. There is a high incidence of bilateral rupture at presentation or subsequent contralateral rupture in affected dogs. Although stifle synovitis increases risk of contralateral CrCLR, relatively little is known about risk factors for subsequent contralateral rupture, or whether therapeutic intervention may modify this risk.

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.

Role of calcitonin gene-related peptide in bone repair after cyclic fatigue loading.

Background: Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone loading, particularly fatigue loading.

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).

Systemic effects of ulna loading in male rats during functional adaptation.

Functional skeletal adaptation is thought to be a local phenomenon controlled by osteoctyes. However, the nervous system also may have regulatory effects on adaptation. The aim of this study was to determine the effects of loading of a single bone on adaptation of other appendicular long bones and whether these responses were neuronally regulated.

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.

The effect of early hyaluronic acid delivery on the development of an acute articular cartilage lesion in a sheep model.

Background: Partial-thickness articular cartilage lesions occur with knee trauma and may progress to osteoarthritis. This study evaluates the effectiveness of hyaluronic acid on cartilage healing after acute knee injury in sheep.

Hypothesis: Early administration of hyaluronic acid to an acute cartilage injury will prevent chondrocyte death and improve cartilage metabolism.

Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age).

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.

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.

Comparison of techniques for determination of chondrocyte viability after thermal injury.

Objective: To compare 2 methods of quantitating chondrocyte viability and to determine chondrocyte response to thermal injury over time.

Sample Population: 108 stifle joints from 54 adult rats.

Procedures: Cartilage from the distal aspect of the femur was treated ex vivo with radiofrequency energy at a probe setting that would result in immediate partial-thickness chondrocyte death; untreated sections served as controls.

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.

Inflammatory changes in ruptured canine cranial and human anterior cruciate ligaments.

Objective: To compare expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K and histologic changes in canine cranial cruciate ligaments (CCLs) and human anterior cruciate ligaments (ACLs).

Study Population: Sections of cruciate ligaments from 15 dogs with ruptured CCLs, 8 aged dogs with intact CCLs, 14 human beings with ruptured ACLs, and 11 aged human beings with intact ACLs.

Procedure: The CCLs and ACLs were evaluated histologically, and cells containing TRAP and cathepsin K were identified histochemically and immunohistochemically, respectively.