Hepatocyte growth factor/scatter factor is not a potent regulator of anabolic and catabolic gene expression in adult human articular chondrocytes.
Objective. Hepatocyte growth factor (HGF) has been reported to be present in articular cartilage and to be a potentially important inducing factor of anabolic and catabolic activity in chondrocytes. The aim of this study was to determine the expression levels of full length-functional-hgf and its receptor c-met in normal and osteoarthritic cartilage and the effect of HGF on anabolic and catabolic gene expression in adult human articular chondrocytes. Methods. Isolated adult human articular chondrocytes were stimulated for 48h with HGF (1, 10, and 100ng/ml). Synthesis of proteoglycans was determined by [(35)S]sulfate incorporation. mRNA levels for anabolic and catabolic genes as well as c-met and (functional) hgf were quantified using real-time PCR. Additionally, in situ mRNA expression levels of hgf and c-met were quantitatively measured from RNA directly isolated from normal and osteoarthritic adult human articular cartilage. Results. Proteoglycan synthesis in adult human articular chondrocytes was not stimulated by HGF nor was a selection of catabolic genes (collagenases and aggrecanases). Normal adult articular chondrocytes expressed only very low levels of hgf mRNA. Slightly higher levels of hgf were detected in chondrocytes isolated from osteoarthritic cartilage. Significant c-met expression was detected in both sample types. Conclusion. Despite the expression of its receptor c-met and its presence in articular cartilage, HGF does not appear to be a potent player in cartilage matrix turnover, at least not in terms of anabolic and catabolic gene expression in normal adult articular cartilage.
Bau
Brigitte
B
Osteoarticular and Arthritis Research, Department of Pathology, University of Erlangen-Nürnberg, Erlangen D-91054, Germany.
McKenna
Louise A
LA
Soeder
Stephan
S
Fan
Zhiyong
Z
Pecht
Anja
A
Aigner
Thomas
T
D000328:Adult; D000368:Aged; D002102:Cadaver; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*
D007375:Interleukin-1; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D019859:Proto-Oncogene Proteins c-met