W. Knudson et al., Hyaluronan oligosaccharides perturb cartilage matrix homeostasis and induce chondrocytic chondrolysis, ARTH RHEUM, 43(5), 2000, pp. 1165-1174
Objective. To determine the role of CD44-mediated matrix assembly in mainta
ining 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 mat
rix, activation of gelatinolytic activity, and exhibition of the NITEGE epi
tope, 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. Th
e close interaction of chondrocytes with their matrix and their ability to
"sense" changes in receptor occupancy are needed for maintenance of cartila
ge homeostasis.