Normal expression of type 1 insulin-like growth factor receptor by human osteoarthritic chondrocytes with increased expression and synthesis of insulin-like growth factor binding proteins.
OBJECTIVE
Our previous research demonstrated that, in contrast to normal chondrocytes, human osteoarthritic (OA) chondrocytes were hyporesponsive to stimulation by insulin-like growth factor 1 (IGF-1). The aim of the present investigation was to examine whether this finding was due to an alteration in the level of IGF receptors (IGFRs) and/or IGF binding proteins (IGFBP).


METHODS
A quantitative reverse transcriptase polymerase chain reaction technique (RT-PCR) was used to measure the type 1 IGFR messenger RNA (mRNA) level, and Northern blotting was used to measure type 2 IGFR and IGFBP mRNA levels. Western immunoblotting was used to identify and measure IGFBP levels.


RESULTS
There were similar levels of type 1 IGFR mRNA in normal and OA chondrocytes. The level of type 2 IGFR mRNA, in which an increased amount of which can interfere with the biologic effects of IGF-1, was lower in OA chondrocytes compared with normal chondrocytes. Articular chondrocytes produced IGFBP-2, IGFBP-3, and IGFBP-4, and OA chondrocytes secreted and expressed higher amounts than did normal chondrocytes. There was also an increased level of IGFBP-3 in the OA chondrocyte lysates. IGFBPs 1, 5, and 6 were not detectable.


CONCLUSIONS
OA chondrocytes synthesize and express a larger amount of 3 IGFBPs. This observation, along with a lack of detectable change in type 1 IGFR mRNA level, suggests that the hyporesponsiveness of OA chondrocytes to IGF-1 might implicate the involvement of IGFBPs in this pathologic process.
Tardif
G
G
University of Montreal, Quebec, Canada.
Reboul
P
P
Pelletier
J P
JP
Geng
C
C
Cloutier
J M
JM
Martel-Pelletier
J
J
D000368:Aged; D001483:Base Sequence; D015152:Blotting, Northern; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism*
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1