No abstract

Canine hip dysplasia is a common developmental inherited trait characterized by hip laxity, subluxation or incongruity of the femoral head and acetabulum in affected hips. The inheritance pattern is complex and the mutations contributing to trait expression are unknown. In the study reported here, 240 microsatellite markers distributed in 38 autosomes and the X chromosome were genotyped on 152 dogs from three generations of a crossbred pedigree based on trait-free Greyhound and dysplastic Labrador Retriever founders. Interval mapping was undertaken to map the QTL underlying the quantitative dysplastic traits of maximum passive hip laxity (the distraction index), the dorsolateral subluxation score, and the Norberg angle. Permutation testing was used to derive the chromosome-wide level of significance at p<0.05 for each QTL. Chromosomes 4, 9, 10, 11 (p<0.01), 16, 20, 22, 25, 29 (p<0.01), 30, 35, and 37 harbor putative QTL for one or more traits. Successful detection of QTL was due to the cross-breed pedigree, multiple-trait measurements, control of environmental background, and marked advancement in canine mapping tools.

Full-thickness canine articular cartilage explants were subjected to compressive loads equivalent to a uniaxial stress of 0.025-1.2 MPa. A single cycle (18 h) of unconfined compression resulted in inhibition of total protein, proteoglycan, and fibronectin synthesis. The inhibition of fibronectin synthesis followed that of total protein synthesis. The magnitude of inhibition increased nonlinearly with increasing load levels. The signal that depressed synthesis remained effective for several hours after removal of load, but by 24 h proteoglycan synthesis had partially recovered and fibronectin and protein synthesis had fully recovered and sometimes exceeded the rate of synthesis in free-swelling controls. Forty-eight hours after five cycles of intermittent unconfined compression with similar loads, proteoglycan content and synthesis did not differ in loaded disks and in disks that were never loaded in vitro. Interestingly, the percentage of water in disks that had never been loaded in vitro increased significantly after 10 days in culture, relative to the percentage of water in free-swelling disks on the day of harvest. Intermittent compressive loading in the range of 0.5-1.2 MPa partially prevented this increase. Our results confirmed the previously reported inhibition of biosynthesis with static loading but also suggested that exposure to intermittent compressive loading may help to maintain the normal ratio of dry to wet weight in the explant.

Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1 5 3 . 5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational level by measuring [3H]-proline incorporation into [3H]-hydroxyproline. Fibronectin mRNA splicing patterns were evaluated with ribonuclease protection assays. Cytotoxicity was studied using erythrosin B dye exclusion. Steady-state levels of type I1 procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentrations were increased from 1 x lo1 to 1 x 10' pg/ml, dropping below 10% of control values by 1 Y lo5 pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 x loR to 1 A lo9 pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 x lo4 and 1 x lo8 pg/ml. Corticosteroid-induced changes in fibronectin isoform levels were evaluated in articular cartilage samples without in vitro culture. The cartilage-specific (V + C)-isoform was suppressed in both normal and inflamed joints by a single intraarticular injection (0.1 mg/kg) of methylprednisolone. Combined, these data indicate that methylprednisolone suppresses matrix protein markers of chondrocytic differentiation. Decreased and altered chondrocyte expression of matrix proteins likely contributes to the pathogenesis of corticosteroid-induced cartilage degeneration.