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 sulfate/polylactosamine chains are deficient on the lumican residing in the matrix of adult articular cartilage, whereas they are present on the lumican residing in the matrix of juvenile cartilage. Under serum-free conditions with either monolayer cultures, agarose cultures, or micromass cultures, the adult chondrocytes synthesized a form of lumican possessing keratan sulfate/polylactosamine chains. Thus, the adult chondrocytes are capable of producing a proteoglycan form of lumican and this appears to be the default synthesis preference. The micromass culture system proved useful for demonstrating 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-1beta to promote the secretion of a form of lumican deficient in keratan sulfate/polylactosamine chains, whereas with bFGF, IGF-1 and TGFbeta keratan sulfate/polylactosamine chains were present, though their size or degree of 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/polylactosamine chains following proteoglycan secretion, but represented a direct effect on synthesis.
Melching
L I
LI
Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada.
Roughley
P J
PJ
D000328:Adult; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism*; D018929:Cell Culture Techniques; D019902:Chondrocytes / Q000737:chemistry / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005270:Femur Head; D000071235:Fibromodulin; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D007632:Keratan Sulfate / Q000737:chemistry / Q000378:metabolism*; D000071234:Lumican; D008875:Middle Aged; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans
D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D016207:Cytokines; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604306:LUM protein, human; D000071234:Lumican; D011509:Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate