Differential regulation of the bone morphogenic protein antagonist chordin in human normal and osteoarthritic chondrocytes.
OBJECTIVE
To investigate the distribution of the bone morphogenic protein (BMP) antagonist chordin in normal and osteoarthritic cartilage and synovial membranes, and its regulation in chondrocytes and synovial fibroblasts by inflammatory and growth factors.


METHODS
Localisation of chordin in tissues was undertaken by immunohistochemistry and gene regulation was determined by real time polymerase chain reaction.


RESULTS
In normal cartilage, chordin was found at low levels (mean (SD), 7.6 (1.3)%), mainly in the very superficial layers. In osteoarthritis, chordin was also found in the superficial layers (8.9 (1.1)%), though at a significantly higher level (24.7 (1.5)%) in the last two thirds of the cartilage. In contrast to normal cells, chordin mRNA and protein levels were significantly downregulated (p<0.01) in osteoarthritic chondrocytes by all the growth factors tested. Interferon gamma stimulated chordin expression in normal but not in osteoarthritic chondrocytes (p<0.0002), while interleukin 1 beta and tumour necrosis factor alpha did not affect the expression level. However, no difference was found in either the distribution or regulation of chordin in normal and osteoarthritic synovial membranes or synovial fibroblasts.


CONCLUSIONS
The differential distribution and regulation of chordin in normal and osteoarthritic cartilage and chondrocytes suggests an involvement of this antagonist in the osteoarthritic process.
Tardif
G
G
Osteoarthritis Research Unit, Hôpital Notre-Dame, Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke Street East, Montreal, Quebec, Canada H2L 4M1.
Pelletier
J-P
JP
Hum
D
D
Boileau
C
C
Duval
N
N
Martel-Pelletier
J
J
D000368:Aged; D000077214:Becaplermin; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D019902:Chondrocytes / Q000737:chemistry / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D007371:Interferon-gamma; C054234:chordin