The superficial layer of human articular cartilage is more susceptible to interleukin‐1–induced damage than the deeper layers

Abstract

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 %-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 '251-labeled IL-1.Results. IL-1 induced more severe inhibition of proteoglycan synthesis and a lower ratio of secreted TIMP-kstromelysin in chondrocytes from superficial cartilage than those from deeper cartilage. IRAP blocked responses to IL-1 more effectively in chondro- Submitted for publication April 10, 1995; accepted in revised form September 22, 1995.cytes from deep cartilage than those from superficial cartilage. Chondrocytes from the articular surface showed approximately twice the number of high-mity binding sites for IL-1 as did cells from deep cartilage.Conclusion. Chondmytes 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.Treatment of cartilage tissue in vitro with IL-1 (1,2) or injection of IL-1 into the synovial cavity (3,4) results in inhibition of synthesis of proteoglycans (PGs) (5-9), enhanced production of prostaglandin E2 (PGE,) (10) and metalloproteinases (1 l), and excessive catabolism of PGs. Together these conditions contribute to loss of cartilage matrix and inadequate tissue repair. Based on experimental results and on the finding of IL-1, PG fragments, and proteolytic enzymes in inflamed joints (12)(13)(14), it is widely accepted that IL-1 plays an important role in cartilage erosion in inflammatory joint diseases. Because PG synthesis is usually upregulated during the early stages of osteoarthritis (15), IL-1 has been given little attention as a potential mediator of early metabolic changes in articular cartilage. In patients, on the other hand, especially during the inflammatory episodes which almost always develop at late stages of the disease, IL-1 appears to play a significant role in suppressing the synthesis and repair mechanism (16). IL-1 a and IL-Ip, the 2 agonist isoforms of 1L-1 (17-21), bind to specific cell-membrane receptors and set in motion complex signal transduction pathways which are not yet fully understood (22). The human recombinant form of IL-1 receptor antagonist protein also binds to the same receptors, but since it fails to initiate signal transduction or elicit biological responses, it blocks cellular ARTICULAR SURFACE SUSCEPTIBILITY TO IL-1 479 responses to IL-1 (23) and acts as a pure antagonist (24)(25)(26)(27)(28).Two structurally related c...

Does Periacetabular Osteotomy Have Depth-related Effects on the Articular Cartilage of the Hip?

“…This confirms the findings of several other authors, indicating depth-related properties and metabolic specialization of the resident chondrocytes leading to characteristic zonal variations in cartilage adaption to mechanical loading [9,36,43]. In addition, the unique depth-dependent features and high vulnerability of the superficial layer have been demonstrated in a study investigating the effect of inflammatory cytokines in different cartilage layers [13]. They reported at least a 10-fold greater concentration of interleukin-1a for a similar inhibition of PG synthesis in cells from the deeper layer compared with the superficial layers.…”

“…Given the importance of the weightbearing status on the biology of chondrocytes [23,31] and the heterogeneous structure of cartilage [7], our study investigated whether the mechanical modulation of the dysplastic joint with a PAO affects the biochemical composition of articular cartilage and whether this effect varies with the depth of cartilage. The superficial cartilage layer has been shown to have a low charge density, low compressive stiffness [8], and to be less protected by inhibitors to degradation [13], which suggest that this region may be more vulnerable. A better understanding of the biologic changes in articular cartilage with a pelvic osteotomy may help us better predict the long-term health of the joint.…”

Activation of Interleukin-1 Signaling Cascades in Normal and Osteoarthritic Articular Cartilage

“…32 Interestingly, some activation of the IL-1␤ pathways was observed in normal cartilage. Presumably, this reflects a constant baseline level of exposure of IL-1␤ in the joint system.…”

Nitric oxide production by superficial and deep articular chondrocytes

“…These differences were detectable not only in terms of oxidant production and NO synthase activity, but also at the transcriptional level, which suggests that this feature represents still-another phenotypic difference between superficial and deep cells, in addition to the morphologic characteristics, synthetic activities (10,(25)(26), and response to cytokines (28,29).…”