Modulation of keratan sulfate synthesis on lumican by the action of cytokines on human articular chondrocytes

Adult human articular chondrocytes were used to investigate why keratan sul fate/polylactosamine chains are deficient on the lumican residing in the ma trix of adult articular cartilage, whereas they are present on the lumican residing in the matrix of juvenile cartilage. Under serum-free conditions w ith either monolayer cultures, agarose cultures, or micromass cultures, the adult chondrocytes synthesized a form of lumican possessing keratan sulfat e/polylactosamine chains. Thus, the adult chondrocytes are capable of produ cing a proteoglycan form of lumican and this appears to be the default synt hesis preference. The micromass culture system proved useful for demonstrat ing that growth factors/cytokines present in the extracellular milieu are: capable of influencing the structure of the keratan sulfate/polylactosamine chains on the secreted lumican. Of particular note was the ability of IL-1 beta to promote the secretion of a form of lumican deficient in keratan su lfate/polylactosamine chains, whereas with bFGF, IGF-1 and TGF beta keratan sulfate/polylactosamine chains were present, though their size or degree o f substitution varied. Thus, growth factors/cytokines are able to modulate the molecular form of lumican. Furthermore, additional studies showed that this modulation was not due to the degradation of keratan sulfate/polylacto samine chains following proteoglycan secretion, but represented a direct ef fect on synthesis. (C) 1999 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.