Expression profiling of metalloproteinases and their inhibitors in cartilage.
OBJECTIVE
To profile the expression of all known members of the matrix metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases (TIMP) gene families in normal cartilage and cartilage from patients with osteoarthritis (OA).


METHODS
Human cartilage was obtained from femoral heads at joint replacement for OA or following fracture to the femoral neck. Total RNA was purified, and gene expression was assayed using quantitative real-time polymerase chain reaction.


RESULTS
Several members of the above gene families were regulated in OA. Genes that showed increased expression in OA were MMP13, MMP28, and ADAMTS16 (all at P < 0.001), MMP9, MMP16, ADAMTS2, and ADAMTS14 (all at P < 0.01), and MMP2, TIMP3, and ADAMTS12 (all at P < 0.05). Genes with decreased expression in OA were MMP1, MMP3, and ADAMTS1 (all at P < 0.001), MMP10, TIMP1, and ADAMTS9 (all at P < 0.01), and TIMP4, ADAMTS5, and ADAMTS15 (all at P < 0.05). Correlation analysis revealed that groups of genes across the gene families were coexpressed in cartilage.


CONCLUSIONS
This is the first comprehensive expression profile of all known MMP, ADAMTS, and TIMP genes in cartilage. Elucidation of patterns of expression provides a foundation with which to understand mechanisms of gene regulation in OA and potentially to refine the specificity of antiproteolytic therapies.
Kevorkian
Lara
L
University of East Anglia, Norwich, UK.
Young
David A
DA
Darrah
Clare
C
Donell
Simon T
ST
Shepstone
Lee
L
Porter
Sarah
S
Brockbank
Sarah M V
SM
Edwards
Dylan R
DR
Parker
Andrew E
AE
Clark
Ian M
IM
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002356:Cartilage / Q000502:physiology*; D019483:Disintegrins / Q000235:genetics; D005260:Female; D005269:Femur / Q000293:injuries; D050723:Fractures, Bone / Q000235:genetics / Q000503:physiopathology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D045726:Metalloproteases / Q000235:genetics*; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000235:genetics* / Q000503:physiopathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
D019483:Disintegrins; D019714:Tissue Inhibitor of Metalloproteinases; D045726:Metalloproteases; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D008666:Metalloendopeptidases