A role for the interleukin-1 receptor in the pathway linking static mechanical compression to decreased proteoglycan synthesis in surface articular cartilage

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Abstract

Loading of articular cartilage during weight bearing is essential for the maintenance of cartilage function. Although certain cyclic loading protocols stimulate extracellular matrix synthesis, constant or static compression decreases proteoglycan and collagen synthesis in cartilage explants. The goal of this study was to determine whether the compression-induced decrease in proteoglycan synthesis involves an interleukin-1 (IL-1) signaling pathway. Cartilage explants were compressed 50% in the presence of IL-1 receptor antagonist (IL-1ra), and the incorporation of [35S]sulfate into macromolecules was measured. IL-1ra increased sulfate incorporation in compressed cartilage but not in cartilage maintained at the in situ thickness (0% compression). IL-1α and IL-1β mRNAs were detected in cartilage compressed 50% for at least 3 h, while nitric oxide synthase II mRNA was only detected in cartilage compressed 50% for 6 h. The data support a role for the IL-1 receptor in the pathway linking static compression to reduced proteoglycan synthesis.

Section snippets

Specialized materials

Cartilage disks were subjected to static compression using chambers that have been previously described [13]. Human recombinant IL-1ra was from R&D Systems. Human recombinant IL-1α was provided by the Biological Resources Branch of the National Cancer Institute.

Cartilage explant culture

Cartilage cores (4-mm diameter) were taken from radiocarpal joints of 2-week-old calves, and uniform 1-mm-thick disks were cut from the articular surface. The disks of surface cartilage were washed in phosphate-buffered saline and placed

Kinetics of the biosynthetic response to static compression and exogenous IL-1α

Proteoglycan biosynthesis decreases in IL-1-stimulated and mechanically compressed bovine articular cartilage, and the time courses of the responses to these stimuli were compared. Sulfate incorporation decreased approximately 4 h after IL-1 stimulation or mechanical compression (Fig. 1). Sulfate incorporation during the 1-h pulse labeling period following either 4 or 6 h of exposure to human recombinant IL-1α decreased by approximately 30%. Similarly, static compression to 0.5-mm thickness (50%

Discussion

Considerable experimental evidence indicates that static mechanical compression inhibits cartilage extracellular matrix biosynthesis. Because IL-1 and static compression have similar antianabolic effects on cartilage, we examined whether IL-1 signaling pathways(s) are activated by the static compression protocol. IL-1ra counteracts the inhibition of proteoglycan synthesis that occurs in mechanically compressed surface articular cartilage explants. IL-1ra is a naturally occurring competitive

Acknowledgements

This work was supported by NIH Grant 1 RO3 AG16885-01 and Grant 99-020 from the Orthopaedic Research Education Foundation.

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  • Cited by (0)

    1

    Current address: Department of Orthopaedic Surgery, Tokyo Women’s Medical University, Tokyo, Japan.

    2

    Current address: Department of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY.

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