Hyaluronan oligosaccharides perturb cartilage matrix homeostasis and induce chondrocytic chondrolysis

Objective To determine the role of CD44‐mediated matrix assembly in maintaining cartilage homeostasis. Methods Articular cartilage tissue slices as well as isolated chondrocytes were treated with hyaluronan (HA) hexasaccharides. Tissues and cells were processed for histology, immunohistochemistry, colorimetric assay, reverse transcriptase–polymerase chain reaction, and zymography. Results HA oligosaccharides induced a dose‐dependent state of chondrocytic chondrolysis, including near‐total loss of stainable proteoglycan‐rich matrix, activation of gelatinolytic activity, and exhibition of the NITEGE epitope. However, HA oligosaccharides also induced an increase of proteoglycan synthesis, including elevation of aggrecan and HA synthase 2 messenger RNA. Conclusion Uncoupling chondrocytes from the matrix results in deleterious changes in matrix structure and modifications in chondrocyte metabolism. The close interaction of chondrocytes with their matrix and their ability to “sense” changes in receptor occupancy are needed for maintenance of cartilage homeostasis.