Biochem Pharmacol
December 2007
Interleukin-1 (IL-1) has pleiotropic effects in cartilage. The interferon-induced, double stranded RNA-activated protein kinase PKR that phosphorylates eukaryotic initiation factor 2 (eIF2) alpha has been implicated in cytokine effects in chondrocytes. A compound was recently identified that potently suppresses PKR autophosphorylation (IC50 approximately 200 etaM) and partially restores PKR-inhibited translation in a cell-free system with significant effect in the nanomolar range.
View Article and Find Full Text PDFChondrocytes in situ experience fluctuations in extracellular osmolarity resulting from mechanical loading. The objective of this study was to determine whether hyperosmotic stress causes or exacerbates interleukin-1 (IL-1)-mediated effects in bovine articular cartilage. Disks of cartilage cut from the articular surface of calf radiocarpal joints were incubated for 24h in the presence or absence of IL-1 in Dulbecco's modified Eagle's medium adjusted to various osmolalities with sucrose or NaCl.
View Article and Find Full Text PDFObjective: In recent years it has become evident that tissue cyclooxygenase-2 (COX-2) may play a role in carcinogenesis and tumor malignancy. There is now a mounting body of information that strongly implies that COX-2 inhibitors may be of some value in the management of patients with carcinomas, and most recently several similar reports have appeared relating to sarcomas.
Methods: The authors studied 32 samples of cartilage tumors from our tumor tissue bank for the presence of COX-2 by a Western blot technique.
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.
View Article and Find Full Text PDFThe objective of the current study was to determine whether the balance of interleukin-1 and intracellular interleukin-1 receptor antagonist in chondrocytes in osteoarthritic human joints favors agonist action. Chondrocytes were isolated from cartilage specimens taken at the time of joint arthroplasty. Interleukin-1alpha, interleukin-1beta, and intracellular interleukin-1 receptor antagonist messenger ribonucleic acids were assessed by reverse transcriptase-polymerase chain reaction, and chondrocyte lysates were analyzed by enzyme-linked immunosorbent assay for the respective proteins.
View Article and Find Full Text PDFOsteoarthritis (OA) is a disabling joint disease for which there is currently no cure. It is characterized by the destruction of articular cartilage. One strategy that is being explored for protecting the cartilage in OA is the administration of transforming growth factor-beta, which in vitro antagonizes cartilage degradation initiated by catabolic stimulants such as interleukin-1 (IL-1).
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