Fibronectin fragments cause chondrolysis of bovine articular cartilage slices in culture.

High molecular weight hyaluronan promotes repair of IL-1β-damaged cartilage explants from both young and old bovines

“…Fn-fs were generated from human Fn as described 24 . The Fn-f tested was a well-characterized amino-terminal 29-kDa Fn-f that has been found to be the most potent 24 and is referred to as the Fn-f.…”

“…The total amount of PG/mg wet weight cartilage was determined by assays with dimethylmethylene blue (DMB) reagent after treatment of 50-80 mg of cartilage in 1.0 ml of 50 mM phosphate buffer, pH 6, containing 10 mM EDTA and 10 mM cysteine, with 50 µg/ml papain for 16 h at 65°C as originally described [25][26][27] . To assay PG, a volume of 0.8 ml DMB reagent, prepared as described 24 , was mixed with 190 µl of 1.37 M GuHCl and 10 µl of test sample. After 2 min, a spectrophotometer was used to determine absorbances at 525 and 595 nm, using water as a blank.…”

“…In our investigation of the mechanisms by which HA suppresses cartilage damage, we have utilized a model of cartilage damage involving the ability of fibronectin fragments (Fn-f) to damage cartilage explants 24,25 , through elevation of catabolic cytokines 26,27 . This, in turn, elevates levels of MMPs [27][28][29] and also induces aggrecanase-like cleavage 30 .…”

Mixtures of glucosamine and chondroitin sulfate reverse fibronectin fragment mediated damage to cartilage more effectively than either agent alone

“…In order to investigate whether or not GluNH 2 and CS as single agents or as a combination at concentrations close to those observed after oral ingestion are effective, we have tested the GluNH 2 hydrochloride and the CS used in the GAIT study 16 and also tested in other studies 16,17,28,29 , in a cartilage chondrolytic culture model in which the catabolic mediators, fibronectin fragments (Fn-fs), are added to cartilage explants 50 . The Fn-fs elevate catabolic cytokines 51,52 and MMPs 51,53 which cause transient suppression of PG synthesis and severe depletion of cartilage PG 54 .…”

Platelet-Rich Plasma Attenuates 30-kDa Fibronectin Fragment–Induced Chemokine and Matrix Metalloproteinase Expression by Meniscocytes and Articular Chondrocytes

“…22 Unlike intact FN, these FN-f have catabolic activity. 21 FN-f bind to and penetrate cartilage tissue, resulting in proteinase expression and cartilage damage. 60 FN-f show potent catabolic activity in increasing expression of Toll-like receptors and inflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-1a; elevating production of matrix metalloproteinase (MMP) proteases; and suppressing proteoglycan synthesis.…”