Clusterin expression in adult human normal and osteoarthritic articular cartilage.
OBJECTIVE
To characterize the expression pattern of clusterin in adult human normal and osteoarthritic cartilage.


METHODS
Clusterin mRNA expression in adult human normal and osteoarthritic cartilage was investigated by analysis of cDNA libraries, TaqMan quantitative RT-PCR, microarray and in situ hybridization.


RESULTS
Sequence analysis of ESTs from adult human normal and osteoarthritic cartilage cDNA libraries demonstrated that the abundance of clusterin in these libraries was equivalent to genes which have been more commonly associated with cartilage. To examine tissue distribution, TaqMan Quantitative PCR analysis was performed using RNA from a panel of individual normal tissues. Clusterin was expressed at significant levels in cartilage, brain, liver, and pancreas. The expression of clusterin mRNA was up-regulated in early osteoarthritic vs normal cartilage when analysed by microarray analysis. Using in situ hybridization, chondrocytes of normal cartilage expressed moderate levels of clusterin. Upper mid-zone chondrocytes in cartilage with early stages of osteoarthritic disease expressed high levels of clusterin mRNA. In advanced osteoarthritic cartilage, the overall expression of clusterin was reduced.


CONCLUSIONS
The induction of clusterin has been associated with a variety of disease states where it appears to provide a cytoprotective effect. The increased expression of clusterin mRNA in the early stages of osteoarthritis (OA) may reflect an attempt by the chondrocytes to protect and repair the tissue. In contrast, the decrease in clusterin mRNA in the advanced osteoarthritic cartilage accompanies the final degenerative stages of the disease. An understanding of the expression of clusterin in osteoarthritis may allow consideration of this protein as a marker for cartilage changes in this chronic degenerative condition.
Connor
J R
JR
Department of Musculoskeletal Diseases, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. Janicr_R_Connor@gsk.com
Kumar
S
S
Sathe
G
G
Mooney
J
J
O'Brien
S P
SP
Mui
P
P
Murdock
P R
PR
Gowen
M
M
Lark
M W
MW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism*; D016022:Case-Control Studies; D051152:Clusterin; D005260:Female; D015723:Gene Library; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010003:Osteoarthritis / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D011509:Proteoglycans; D012333:RNA, Messenger