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.


CONCLUSIONS
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.
Knudson
W
W
Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612-3864, USA.
Casey
B
B
Nishida
Y
Y
Eger
W
W
Kuettner
K E
KE
Knudson
C B
CB
D053674:Aggrecans; D000464:Alginates; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002358:Cartilage, Articular / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D006820:Hyaluronic Acid / Q000235:genetics / Q000494:pharmacology*; D037181:Lectins, C-Type; D008297:Male; D009844:Oligosaccharides / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D053674:Aggrecans; D000464:Alginates; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D006603:Hexuronic Acids; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D009844:Oligosaccharides; D011509:Proteoglycans; D012333:RNA, Messenger; D020723:Glucuronic Acid; D006820:Hyaluronic Acid