The superficial layer of human articular cartilage is more susceptible to interleukin-1-induced damage than the deeper layers.
OBJECTIVE
To compare the responses of chondrocytes from superficial and deep layers of normal human articular cartilage to interleukin-1 (IL-1) and IL-1 receptor antagonist protein (IRAP), and to evaluate the binding sites for IL-1 on these cells.


METHODS
Cartilage and chondrocytes from superficial and deeper layers of human femoral condyles were cultured with and without IL-1 in the presence and absence of IRAP. The effect of these agents on 35S- proteoglycan synthesis and catabolism and production of stromelysin and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by biochemical and immunologic assays. Receptor binding was evaluated using 125I-labeled IL-1.


RESULTS
IL-1 induced more severe inhibition of proteoglycan synthesis and a lower ratio of secreted TIMP-l:stromelysin in chondrocytes from superficial cartilage than those from deeper cartilage. IRAP blocked responses to IL-1 more effectively in chondrocytes from deep cartilage than those from superficial cartilage. Chondrocytes from the articular surface showed approximately twice the number of high-affinity b!nding sites for IL-1 as did cells from deep cartilage.


CONCLUSIONS
Chondrocytes from the surface of articular cartilage show a greater vulnerability to the harmful effects of IL-1 and are less responsive to the potential therapeutic effects of IRAP than cells in the deeper layers of the tissue.
Hauselmann
H J
HJ
Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
Flechtenmacher
J
J
Michal
L
L
Thonar
E J
EJ
Shinmei
M
M
Kuettner
K E
KE
Aydelotte
M B
MB
D000293:Adolescent; D000328:Adult; D002358:Cartilage, Articular / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D008875:Middle Aged; D011509:Proteoglycans / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011509:Proteoglycans; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins