The regional sensitivity of chondrocyte gene expression to coactive mechanical load and exogenous TNF-α stimuli.

Both mechanical load and elevated levels of proinflammatory cytokines have been associated with the risk for developing osteoarthritis (OA), yet the potential interaction of these mechanical and biological factors is not well understood. The purpose of this study was to evaluate the response of chondrocytes to the effects of dynamic unconfined compression, TNF-α, and the simultaneous effects of dynamic unconfined compression and TNF-α. The response to these three treatments was markedly different and, taken together, the response in the gene expression of chondrocytes to the different treatment conditions suggest a complex interaction between structure, biology, and mechanical loading.

New insights into the role of the superficial tangential zone in influencing the microstructural response of articular cartilage to compression.

OBJECTIVE: The purpose of this study was to characterize the microstructural response of healthy cartilage in a perturbed physical environment to compressive loading with a novel channel indentation device. Manipulation of the cartilage physical environment was achieved through (1) removal of the superficial tangential zone (STZ) and (2) varying the saline bathing solution concentration. DESIGN: Cartilage-on-bone blocks were subjected to creep loading under a nominal stress of 4.5 MPa via an indenter consisting of two rectangular platens separated by a narrow channel relief space to create a specific region where cartilage would not be directly loaded. Each sample was fixed in its near-equilibrium deformed state, after which the cartilage microstructure was examined using differential interference contrast (DIC) optical microscopy and scanning electron microscopy (SEM). The cartilage bulge in the channel relief space was studied in detail. RESULTS: STZ removal altered the indentation response at the macro- and microstructural levels. Specifically, the strain in the directly compressed regions was reduced (P=0.012) and the bulge height in the channel relief space was greater (P<0.0001) in the STZ-removed compared with the surface-intact samples. The bulge height in the STZ-removed group was always less than the preloaded cartilage thickness. There was intense shear in the non-directly-loaded regions of intact-cartilage but not in STZ-removed cartilage. Bathing solution concentration influenced only the STZ-removed group, where lower concentrations produced significantly abrupt transitions in matrix continuity between the directly compressed and adjacent non-directly-loaded cartilage (P=0.012). CONCLUSIONS: This study showed that while the surface layer was important in distributing loads away from directly-loaded regions, so were other factors such as the matrix fibrillar interconnectivity, swelling potential, and tissue anisotropy.

Central and peripheral region tibial plateau chondrocytes respond differently to in vitro dynamic compression.

OBJECTIVE: The objective of this study was to test the hypotheses that chondrocytes from distinct regions of the porcine tibial plateau: (1) display region-specific baseline gene expression, and (2) respond differently to in vitro mechanical loading. METHODS: Articular cartilage explants were obtained from central (not covered by meniscus) and peripheral (covered by meniscus) regions of porcine tibial plateaus. For baseline gene expression analysis, samples were snap frozen. To determine the effect of mechanical loading, central and peripheral region explants were exposed to equivalent dynamic compression (0-100 kPa) and compared to site-matched free-swelling controls (FSCs). mRNA levels for type II collagen (CII), aggrecan (AGGR), matrix metalloproteinase 1 (MMP-1), MMP-3, MMP-13, A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAM-TS4), ADAM-TS5, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, and tumor necrosis factor alpha (TNFalpha) were quantified using real time polymerase chain reaction (RT-PCR). RESULTS: At baseline, mRNA levels for the structural proteins CII and AGGR were approximately twofold greater in the central region compared with peripheral region explants. In vitro dynamic compression strongly affected expression levels for CII, AGGR, MMP-3, and TIMP-2 relative to FSCs. Response differed significantly by region, with greater upregulation of CII, AGGR, and MMP-3 in central region explants. CONCLUSIONS: Chondrocytes from different regions of the porcine tibial plateau express mRNA for structural proteins at different levels and respond to equivalent in vitro mechanical loading with distinctive changes in gene expression. These regional biological variations appear to be related to the local mechanical environment in the normal joint, and thus may indicate a sensitivity of the joint to conditions that alter joint loading such as anterior cruciate ligament (ACL) injury, meniscectomy, or joint instability.