Superficial zone chondrocytes from bovine articular cartilage respond predominately to HA oligosaccharides

INTRODUCTION: Articular chondrocytes exhibit an extensive hyaluronan (HA) and proteoglycan-rich pericellular matrix that is tethered to the cell surface via interactions with the HA receptor, CD44. One hallmark of osteoarthritic cartilage is the loss of proteoglycan from the extracellular matrix. This may represents the disruption of proteoglycan/HA-chondrocyte interactions. One of our experimental approaches to mimic a loss of cell-matrix interaction is to use HA oligosaccharides (HAoligos) as specific HA antagonists in cartilage explants or chondrocyte cultures. HAoligos can displace high molecular weight HA from its principal receptor CD44 in a competitive manner. The uncoupling of HA from CD44 gives rise to signal transduction events; in articular chondrocytes we have found that cell signaling induces both the stimulation of genes involved in matrix degradation/remodeling such as MMPs as well as matrix repair genes including collagen type II, aggrecan, and HAS-2 [1, 2]. Articular cartilage is a stratified tissue with well characterized depth-dependent patterns of cellular morphology, extracellular matrix ultrastructure, and material properties. Previous studies have reported significant phenotypic differences between superficial zone chondrocytes and middle/deep zone chondrocytes in regards to cell size, matrix gene expression, and extracellular matrix components [3]. We found no report to show the zonal difference in regard to the responses to disruption in the pericellular matrix. It is important to study the zonal difference in the responsiveness to the HA antagonists to understand the pathology and the development of osteoarthritis.