Differential expression of egr-1 in osteoarthritic compared to normal adult human articular cartilage.
OBJECTIVE
The purpose of this study was to identify genes that are differentially expressed in normal versus osteoarthritic human articular cartilage as either potential novel therapeutic targets or diagnostic markers of this disease.


METHODS
mRNA was isolated from histologically normal and osteoarthritic adult human articular cartilage. The Differential Display technique was employed which identified differentially expressed genes in the normal and diseased tissue. Northern and reverse Northern hybridization were used to confirm the gene expression pattern. Immunohistochemistry and in-situ hybridization were used to localize expression of Egr-1 protein and mRNA respectively in cartilage.


RESULTS
A transcription factor, early growth response protein-1 (Egr-1) was found to be down-regulated more than six-fold in multiple human OA cartilage samples when compared to normal tissue. Immunohistochemistry indicated that Egr-1 was expressed throughout normal adult cartilage, in deep-, mid- and superficial-zones. In contrast, in OA cartilage there was expression of Egr-1 mRNA and protein only in the chondrocytes undergoing cloning.


CONCLUSIONS
Egr-1 is differentially expressed in OA versus normal cartilage and because of its role in transcriptional activation and repression and regulation of proliferation, differentiation and apoptosis, Egr-1 may play an important role in the pathogenesis of OA. Up-regulation of Egr-1 may therefore provide a novel therapeutic approach for either the prevention or treatment of OA.
Wang
F L
FL
Department of Bone & Cartilage Biology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Connor
J R
JR
Dodds
R A
RA
James
I E
IE
Kumar
S
S
Zou
C
C
Lark
M W
MW
Gowen
M
M
Nuttall
M E
ME
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation; D051766:Early Growth Response Protein 1; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D005819:Genetic Markers; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors