Objective. To characterize cartilage shear strain during articulation, and the effects of lubrication and degeneration.Methods. Human osteochondral cores from lateral femoral condyles, characterized as normal or mildly degenerated based on surface structure, were selected. Under video microscopy, pairs of osteochondral blocks from each core were apposed, compressed 15%, and subjected to relative lateral motion with synovial fluid (SF) or phosphate buffered saline (PBS) as lubricant. When cartilage surfaces began to slide steadily, shear strain (E xz ) and modulus (G) overall in the full tissue thickness and also as a function of depth from the surface were determined.Results. In normal tissue with SF as lubricant, E xz was highest (0.056) near the articular surface and diminished monotonically with depth, with an overall average E xz of 0.028. In degenerated cartilage with SF as lubricant, E xz near the surface (0.28) was 5-fold that of normal cartilage and localized there, with an overall E xz of 0.041. With PBS as lubricant, E xz values near the articular surface were ϳ50% higher than those observed with SF, and overall E xz was 0.045 and 0.062 in normal and degenerated tissue, respectively. Near the articular surface, G was lower with degeneration (0.06 MPa, versus 0.18 MPa in normal cartilage). In both normal and degenerated cartilage, G increased with tissue depth to 3-4 MPa, with an overall G of 0.26-0.32 MPa.Conclusion. During articulation, peak cartilage shear is highest near the articular surface and decreases markedly with depth. With degeneration and diminished lubrication, the markedly increased cartilage shear near the articular surface may contribute to progressive cartilage deterioration and osteoarthritis.

Abstract-The dystrophin-glycoprotein complex is a large complex of membrane-associated proteins linking the cytoskeleton to the extracellular matrix in muscle. Transmembrane heterodimeric (␣␤) integrins serve also as cellular adhesion molecules and mechanotransducers. In the animal model for Duchenne muscular dystrophy, the mdx mouse, loss of dystrophin causes more severe abnormalities in skeletal than in cardiac muscle. We hypothesized that ablation of cardiac myocyte integrins in the mdx background would lead to a severe cardiomyopathic phenotype. Mdx mice were crossed to ones with cardiac myocyte-specific deletion of ␤1 integrin (␤1KO) to generate ␤1KOmdx. Unstressed ␤1KOmdx mice were viable and had normal cardiac function; however, high mortality was seen in peri-and postpartum females by 6 months of age, when severe myocardial necrosis and fibrosis and extensive dystrophic calcification was seen. Decreased ventricular function and blunted adrenergic responsiveness was found in the ␤1KOmdx mice compared with control (Lox/Lox, no Cre), ␤1KO, and mdx. Similarly, adult ␤1KOmdx males were more prone to isoproterenol-induced heart failure and death compared with control groups. Given the extensive calcification, we analyzed transcript levels of genes linked to fibrosis and calcification and found matrix ␥-carboxyglutamic acid protein, decorin, periostin, and the osteoblast transcription factor Runx2/Cbfa1 significantly increased in ␤1KOmdx cardiac muscle. Our data show that combined deficiency of dystrophin and integrins in murine cardiac myocytes results in more severe cardiomyopathic changes in the stressed myocardium than reduction of either dystrophin or integrins alone and predisposes to myocardial calcification. Key Words: Integrin Ⅲ muscular dystrophy Ⅲ dystrophin Ⅲ heart failure Ⅲ calcification T he cardiac myocyte cytoskeleton and contractile apparatus are tethered to the sarcolemma at specialized regions termed costameres, which are aligned with the Z-disk. 1 Costameres are important for lateral force transmission from the sarcomere to the extracellular matrix (ECM) and from 1 myocyte to the next. 2 Three different cytoskeleton networks comprise the costamere: the dystrophin glycoprotein complex (DGC), the integrins, and the spectrinbased cytoskeleton.The DGC is composed of several membrane-spanning and associated proteins and is enriched in, but not restricted to, costameric regions. 2,3 In muscle, the DGC includes dystrophin, sarcoglycans (␣, ␤, ␥, ␦, , and ), dystroglycans (␣ and ␤), ␣-dystrobrevin, syntrophins (␣1, ␤1 and ␤2), sarcospan, and NO synthase. Dystrophin is a 427-kDa protein that constitutes a core component of the DGC. Mutations in the human dystrophin gene lead to Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, and X-linked dilated cardiomyopathy. 4 In mice, an X-linked recessive mutation in the dystrophin gene (mdx) results in loss of dystrophin expression, destabilization of the DGC, and muscular dystrophy. Whereas cardiomyopathy may occur early in the life of patie...

During joint articulation, cartilage is subjected to compression, shear, and sliding, mechanical factors that regulate and affect cartilage metabolism. The objective of this study was to use an in vitro material-on-cartilage shear test to elucidate the effects of counter-surface roughness (Polished, Mildly rough, and Rough), lubricants (phosphate buffered saline (PBS) and bovine synovial fluid (bSF)), and compression offset on the shearing and sliding of normal human talar cartilage under dynamic lateral displacement. Peak shear stress (σ xz,m ) and strain (E xz,m ) increased with increasing platen roughness and compression offset, and were 30% higher with PBS than with bSF. Compared to PBS, bSF was more effective as a lubricant for P than for M and R platens as indicated by the higher reduction in kinetic friction coefficient (−60% vs. − 20% and −19%, respectively), σ xz,m (−50% vs. −14% and −17%) and E xz,m (−54% vs. −19% and − 17%). Cartilage shear and sliding were evident for all counter-surfaces either at low compression offset (10%) or with high lateral displacement (70%), regardless of lubricant. An increase in tissue shear occurred with either increased compression offset or increased surface roughness. This material and biomechanical test system allow control of cartilage σ xz,m and E xz,m , and hence, sliding magnitude, for an imposed lateral displacement. It therefore can facilitate study of cartilage mechanobiological responses to distinct regimes of cartilage loading and articulation, such as shear with variable amounts of sliding.

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