Osteoarthritis is a common disease of diarthrosis (synovial) joints that is characterized by degeneration of articular cartilage, formation of new bone at joint margins, and pain or loss of function. The osteoarthritic disease process involves the entire synovial joint, which encompasses the synovium, fibrous joint capsule, ligaments, articular cartilage, and underlying bone. Development of OA in hip joints is likely to involve multiple factors, including genetic and nongenetic variables. Nongenetic factors that contribute to OA include nutrition, body weight, and physical factors such as joint mechanics. Dogs maintained on a restricted diet during growth and development are less likely to develop hip subluxation and secondary OA in hip and shoulder joints and lumbar vertebrae than are dogs fed an unrestricted diet.1 Moreover, just as obesity exacerbates OA of hip joints in humans,2,3 dogs with rapid growth and weight gain are more likely to develop severe OA of hip joints than are dogs on restricted feeding.4
Articular cartilage degeneration in dysplastic canine hip joints is defined as secondary OA and is related to hip displacement, which causes impingement of the acetabulum on the femoral head at a site at which the cartilage is prone to lesions.5 The resultant abnormal focal load and stress leads to erosion of articular cartilage and synovial effusion, followed by subchondral sclerosis and osteophyte formation.6 Cartilage degeneration is uncommon in nondysplastic hip joints.
The contribution of genetic factors to susceptibility to OA is increasingly recognized. Various studies in humans (eg, epidemiologic, twin-pair, and sibling-risk studies), including genome-wide–scanning7,8 and candidate-gene9,10 studies, have provided evidence of an important genetic component in the development of OA in human hip joints. The probability of genetic influence on the development of OA in hip and knee joints in humans was estimated to be as high as 65% in a twin study.11,12 A study13 of the inheritance patterns of secondary OA of hip joints in related Labrador Retriever, Greyhound, and crossbreed dogs revealed that the inheritance process was additive, which suggested that dissection of the underlying genetic variation into QTL by use of genetic linkage analysis would be possible. In Portuguese Water Dogs, a QT locus for acetabular osteophyte formation in hip joints has been mapped to CFA03,14 and susceptibility loci for canine hip dysplasia have been mapped to several chromosomes.15,16
In dogs with hip dysplasia, the pathologic process that underlies the development of OA in multiple joints17 is not completely understood, but genetic susceptibility may be involved, and joint biomechanics likely play a major role in the predilection for the development of OA in hip joints. To our knowledge, the role of genetic susceptibility to OA secondary to hip dysplasia has not been elucidated. The incidence and progression of secondary OA in dogs with hip dysplasia vary with breed; large and giant breeds are most at risk.18 Therefore, genetic variation (breed predisposition) and body weight may be involved in the development and severity of OA of hip joints and in the expression of associated clinical signs.
Despite advances in genetic investigations of OA, the origins of cartilage degeneration in OA of humans and other animals are poorly understood, and fundamental questions regarding the precise molecular nature of this complex disease remain unanswered. The objective of the study reported here was to increase understanding of the molecular basis of OA in canine hip joints via identification of QTL for secondary OA of hip joints in dogs from the same pedigree by use of a whole-genome microsatellite scan.
Canis familiaris chromosome
Extended-hip joint radiograph
Polymorphism information content
Quantitative trait loci
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