Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage.
OBJECTIVE
To analyze the differences in gene expression profiles of chondrocytes in intact and damaged regions of cartilage from the same knee joint of patients with osteoarthritis (OA) of the knee.


METHODS
We compared messenger RNA expression profiles in regions of intact and damaged cartilage (classified according to the Mankin scale) obtained from patients with knee OA. Five pairs of intact and damaged regions of OA cartilage were evaluated by oligonucleotide array analysis using a double in vitro transcription amplification technique. The microarray data were confirmed by real-time quantitative polymerase chain reaction (PCR) amplification and were compared with previously published data.


RESULTS
About 1,500 transcripts, which corresponded to 8% of the expressed transcripts, showed > or = 2-fold differences in expression between the cartilage tissue pairs. Approximately 10% of these transcripts (n = 151) were commonly expressed in the 5 patient samples. Accordingly, 114 genes (35 genes expressed in intact > damaged; 79 genes expressed in intact < damaged) were selected. The expression of some genes related to the wound-healing process, including cell proliferation and interstitial collagen synthesis, was higher in damaged regions than in intact regions, similar to the findings for genes that inhibit matrix degradation. Comparisons of the real-time quantitative PCR data with the previously reported data support the validity of our microarray data.


CONCLUSIONS
Differences between intact and damaged regions of OA cartilage exhibited a similar pattern among the 5 patients examined, indicating the presence of common mechanisms that contribute to cartilage destruction. Elucidation of this mechanism is important for the development of effective treatments for OA.
Sato
Tomoo
T
St. Marianna University School of Medicine, Kawasaki, Japan.
Konomi
Koji
K
Yamasaki
Satoshi
S
Aratani
Satoko
S
Tsuchimochi
Kaneyuki
K
Yokouchi
Masahiro
M
Masuko-Hongo
Kayo
K
Yagishita
Naoko
N
Nakamura
Hiroshi
H
Komiya
Setsuro
S
Beppu
Moroe
M
Aoki
Haruhito
H
Nishioka
Kusuki
K
Nakajima
Toshihiro
T
D002358:Cartilage, Articular / Q000737:chemistry* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis
D012313:RNA