Potent inhibition of cartilage biosynthesis by coincubation with joint capsule through an IL‐1‐independent pathway

Abstract

The reason for the increased risk for development of osteoarthritis (OA) after acute joint trauma is not well understood, but the mechanically injured cartilage may be more susceptible to degradative mediators secreted by other tissues in the joint. To establish a model for such interactions, we coincubated bovine cartilage tissue explants together with normal joint capsule and found a profound (~70%) reduction in cartilage proteoglycan biosynthesis. This reduction is due to release by the joint capsule of a heat-labile and nontoxic factor. Surprisingly, while cultured synovium is a canonical source of IL-1, blockade by either soluble IL-1 receptor (sIL-1r) or IL-1 receptor antagonist (IL-1RA) had no effect. Combined blockade of IL-1 and TNF-alpha also had no effect. To support the clinical relevance of the findings, we harvested joint capsule from post-mortem human knees. Human joint capsule from normal adult knee also released a substance that caused a ~40% decrease in cartilage proteoglycan biosynthesis. Furthermore, this inhibition was not affected by IL-1 blockade with either sIL-1r or IL-1RA. These results suggest that joint capsule tissue from a normal knee joint can release an uncharacterized cytokine that potently inhibits cartilage biosynthetic activity by an IL-1 and TNFindependent pathway.

Pristane primed rat T cells enhance TLR3 expression of fibroblast-like synoviocytes via TNF-α initiated p38 MAPK and NF-κB pathways

“…Etanercept (a TNF-α soluble receptor, CPGJ-pharm, China, 25 μg/ml), DB-1 (a mouse anti-rat IFN-γ monoclonal antibody, IgG1, 20 μg/ml) and α-IL-17 antibody (a rabbit anti-rat IL-17 antibody, IgG, Santa Cruz, 20 μg/ml) were administrated to T cell conditioned medium accordingly [25][26][27]. FLS were seeded in 6-well plates at a density of 10 5 /well and incubated with PPT medium or control medium for 24 h with or without the above blocker accordingly, and the isotype-matched IgG control were used as controls.…”

Quantitative proteomics analysis of cartilage response to mechanical injury and cytokine treatment

“…These cytokines are known to upregulate chondrocyte gene expression of various aggrecanases, collagenases and other MMPs, which are hypothesized to contribute to the degradation of cartilage matrix. In complementary in vitro models of acute joint injury [9–11], injurious mechanical compression has been shown to cause chondrocyte apoptosis and necrosis, and to potentiate the effects of cytokine treatment on cartilage matrix degradation.…”

In vitroevaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system

“…To explain the degradative activities of synovium on cartilage it was proposed that tissuebound IL-1 increased the basal proteoglycans degradation on human OA cartilage during co-culture with synovial membrane 53 . Patwari et al 34 suggest that the catabolic pathways in chondrocytes induced during co-culture with cut synovium may be independent of the pro-inflammatory cytokines (IL-I and TNF-a), the inflammatory mediators secreted by synovium probably correspond to heat labile factors with a molecular weight of $20 kDa. In our study, we observed in the sheep model that without LPS, synovial explants added to cartilage explants increased basal expression of PGE 2 and cartilage GAG loss, in agreement with observations made by others using explants isolated from bovine 33 or human 53 joints.…”

“…Few efficacy studies of chondroprotective drugs used co-culture model of cartilage and synovial tissue 51,52 although it is well established that during in vitro culture, co-incubation of synovial membrane with cartilage generates soluble factors which accelerate matrix degradation [32][33][34] . To explain the degradative activities of synovium on cartilage it was proposed that tissuebound IL-1 increased the basal proteoglycans degradation on human OA cartilage during co-culture with synovial membrane 53 .…”

“…We introduced a co-culture model of cartilage explant with synovial tissue to measure whether and to what extent capsular tissue changes the outcomes of S-(þ)-ibuprofen treatment on activated cartilage since previous studies had demonstrated the degradative capacity of synovium which promotes the catabolic pathways of chondrocytes during co-culture experiments [32][33][34] . We supposed that during in vitro efficacy studies of a drug, the procatabolic environment created during co-culture may have effects on activities of a drug on cartilage degradation.…”