Increased insulin-like growth factor 1 production by human osteoarthritic chondrocytes is not dependent on growth hormone action.
OBJECTIVE
To investigate insulin-like growth factor 1 (IGF-1) production in normal and osteoarthritis (OA) chondrocytes and to further examine the role of growth hormone (GH) in adult human cartilage and, in particular, in diseased tissue.


METHODS
IGF-1 production was measured with a radioimmunoassay. Binding assay, Northern blot, and reverse transcriptase polymerase chain reaction (RT-PCR) techniques were used for GH receptor (GHR) detection. The biological response to GH was estimated via IGF-1 production.


RESULTS
We observed that basal levels of IGF-1 production were significantly higher in OA chondrocytes than in normal cells (P < 0.005). Adult human chondrocytes, however, were unresponsive to GH stimulation with regard to IGF-1 production, as shown in dose-response (0-1,000 ng/ml) and time-course (days 1-8) studies. In addition, no specific 125I-GH binding was detected in either cell type. Northern blot analysis revealed a 5.5-kb GHR messenger RNA (mRNA) species, but semiquantitative RT-PCR revealed no difference in GHR mRNA expression by normal and OA chondrocytes.


CONCLUSIONS
This study indicates that the elevated synthesis of IGF-1 by adult human OA chondrocytes occurs through a GH/GHR-independent mechanism, suggesting that other factors are capable of controlling local IGF-1 production in these cells.
Doré
S
S
University of Montreal, Quebec, Canada.
Abribat
T
T
Rousseau
N
N
Brazeau
P
P
Tardif
G
G
DiBattista
J A
JA
Cloutier
J M
JM
Pelletier
J P
JP
Martel-Pelletier
J
J
D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000032:analysis
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone