Degenartive Joint Disease (DJD) in Horses

Source Text:

Proceedings ACVS Symposium.Florida. 1997 p 96-101
ETIOLOGIES FOR DEGENERATIVE JOINT DISEASE

Sheila Laverty MVB, Diplomate ACVS & ECVS, Université de Montreal, Canada

The condition generally starts with trauma and ends with soft, yellow, fibrillated and ulcerated cartilage, eburnation and sclerosis of the subchondral bone, hyperplasia of the synovial membrane and a thickened fibrous joint capsule, periarticular osteophytes, osteolysis, ankylosis in low motion joints and a decreased range of motion in high motion joints. The article explains that fibrillation in the superficial zone of the articular cartilage occurs initially and may progress as vertical fissures into the deeper layers. Horizontal separation may occur at the osteochondral junction, resulting in separation of the cartilage from the subchondral bone, due to shear forces. Chondrocytes may multiply and form blood capsules in areas of injury. In advanced cases, there may be a breach of the subchondral plate and invasion of the cartilage by granulation tissue and blood vessels.

A primary event is an imbalance in the normal synthesis and degradation of the extracellular matrix by chondrocytes. A loss of proteoglycans (PG) from the cartilage matrix and increased degradation of type II collagen will occur. Increased synthesis of PG and type II collagen also takes place, reflecting an attempt at repair. Accelerated enzymatic degradation results in an overall loss of PG from the matrix. (The as-yet- unidentified enzyme has been termed aggrecanase. Degradation of the type II collagen meshwork by collagenases begins in the superficial areas and in pericellular zones implicating chondrocyte derived proteases as the instigators of these events.

On the cellular level, resident chondrocytes, synoviocytes and infiltrating neutrophils (in cases of septic arthritis) are the major contributors to equine DJD. The cells orchestrate this by means of increased or induced production of cytokines, enzymes, arachidonic acid metabolites and oxygen-derived free radicals (ODFRs), among other things. These products contribute to the cartilage matrix degradation and further augment the cellular response.

The article explains that cytokines, which are produced by both resident and infiltrating cells, are protein intercellular messengers which influence the function of the target cell by exerting a positive or negative effect on gene expression. Interleukin-1 (IL-1) and tumor necrosis factor a (TNFa), both identified in equine joints, are the principal catabolic cytokines which contribute to degradation of the cartilage matrix by inducing cellular production of matrix metalloproteases (MMPs).

The MMPs (collagenases, gelatinases and stromelysins) are the cartilage proteinases that are hypothesized to degrade the cartilage matrix in DJD. Equine chondrocytes and synoviocytes produce stromelysin. The collagenases include MMP-I, MMP-8 and MMP-13. These collagenases can cleave all 3 chains of type II collagen at a specific site in the collagen triple helix, which subsequently unwinds and becomes susceptible to further degradation by these enzymes and gelatinases.

Prostaglandin E2 (PGE2), a metabolite of arachidonic acid, is synthesized and released by equine synoviocytes and chondrocytes and enhances inflammation. It does not appear to have a role in direct matrix degradation. Both neutrophils and chondrocytes may produce oxygen-derived free radicals (ODFRS) which can oxidize membranes, degrade hyaluronan, collagens and PGs in the joint. Cells and extracellular fluids contain free radical scavengers and antioxidants to counteract these effects, but in certain situations they may be overwhelmed. Substance P, a pro-inflammatory peptide, has been detected in various tissues of the healthy equine joint and also in equine osteophytes and erosion channels in DJD.

Equine DJD has different patterns of etiology, depending on the horse’s use, age, and joint. This is related to the biomechanical stresses to which the horse is subjected during different training regimens. DJD may be categorized based on etiology and thus facilitate understanding of the disease in light of the various mechanisms of joint response to injury.

Acute macro trauma includes acute intra-articular fractures, traumatic articular cartilage and ligament injuries. An acute impact load can cause direct disruption of the cartilage matrix. This includes collagen ultrastructural damage and loss of PGs and an immediate inflammatory response with an influx of infiltrating cells. Chronic microtrauma includes synovitis, capsulitis, subchondral bone injury and disease, fragmentation of the distal patella, conformational problems. It is probably the most common cause of DJD in the equine athlete. The chondrocyte responds to repetitive mechanical stress by increasing PG synthesis, but when the stress is too great synthesis decreases.

In the racehorse, fatigue of muscles contributing to joint stability may cause temporary overload in certain areas of the joint towards the end of a race resulting in focal injury. During maximum load, in joints prone to hyperextension (carpus and metacarpophalangeal joint) the trauma is concentrated on the dorsum of the joint. Osteochondral fractures of the carpal bones are an example of such an injury. In addition the articular cartilage of the dorsal sites in the carpal bones is thinner than at central sites and may result in an increased strain on cartilage at these sites. In the unconditioned joint, the effects of such fatigue are probably greater, and thus the training schedule is a decisive factor in the development of joint disease. Repeated trauma to the synovial membrane and joint capsule is the probable cause of chronic synovitis and capsulitis; this may eventually result in DJD. High intra-articular pressures (IAP) have been recorded in metacarpophalangeal joints with synovitis. Due to decreased blood flow, high IAPs may cause hypoxia and acidosis thus interfering with normal balanced joint metabolism. At the time of maximal loading in the carpal joints, maximal joint congruity serves to effectively dissipate the load. Fatigue and speed could interfere with this mechanism and result in ineffective load transmission to the soft tissues and subchondral bone and a concentration of forces in the cartilage leading to injury.

In osteochondrosis the cartilage matrix of the joint is altered, either primarily or secondarily. Due to a weakened matrix, the chondrocytes are easily damaged and in many cases the subchondral bone may be exposed with a release of inflammatory cytokines. An incongruent joint surface may cause focal overloading of the cartilage and abrasion. Fragments of cartilage matrix are associated with a synovitis that, in some cases, could amplify the matrix degradation. These conditions do not always lead to DJD, since juvenile cartilage has an ability to heal. The development of DJD depends on the severity of the condition and the treatment measures that are instigated.

Septic arthritis, if inappropriately treated, can lead to rapid joint destruction because of the precipitation of acute severe inflammation. Early in the disease, macrophages and neutrophils are recruited and together cause rapid matrix destruction by proteolytic enzyme, cytokine and free radical release. The inciting bacteria also produce degradative enzymes and by-products, such as LPS, which further exacerbate the insult and can cause direct chondrocyte death. This, combined with matrix destruction and decreased PG synthesis and normal weight bearing, will lead to a rapidly dysfunctional joint and DJD. Reactive arthritis may also occur as a result of the continued presence of bacterial antigens or LPS in the joint, perpetuating the destructive inflammatory processes.