Zonal gene expression of chondrocytes in osteoarthritic cartilage.
OBJECTIVE
To determine the chondrocyte metabolism in respective zones of osteoarthritic (OA) cartilage.


METHODS
OA cartilage was obtained from macroscopically intact areas of 4 knee joints with end-stage OA. The cartilage was divided into 3 zones, and gene expression profiles were determined in the respective zones by a custom-designed microarray that focused on chondrocyte-related genes. For the genes whose expression was significantly different among the zones, the expression was compared between OA and control cartilage in the respective zones by an analysis using laser capture microdissection and real-time polymerase chain reaction (PCR). For some genes, the correlation of expression was investigated in specific cartilage zones.


RESULTS
A total of 198 genes (approximately 40% of those investigated) were found to be expressed at significantly different levels among the zones. Expression of 26 of those genes was evaluated by laser capture microdissection and real-time PCR, which confirmed the validity of microarray analysis. The expression of cartilage matrix genes was mostly enhanced in OA cartilage, at similar levels across the zones but at different magnitudes among the genes. The expression of bone-related genes was induced either in the superficial zone or in the deep zone, and positive correlations were found among their expression in the respective zones. The expression of 5 proteinase genes was most enhanced in the superficial zone, where their expression was correlated, suggesting the presence of a common regulatory mechanism(s) for their expression.


CONCLUSIONS
In OA cartilage, the metabolic activity of chondrocytes differed considerably among zones. Characteristic changes were observed in the superficial and deep zones.
Fukui
Naoshi
N
Clinical Research Center, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan. n-fukui@sagamihara-hosp.gr.jp
Miyamoto
Yoshinari
Y
Nakajima
Masahiro
M
Ikeda
Yasuko
Y
Hikita
Atsuhiko
A
Furukawa
Hiroshi
H
Mitomi
Hiroyuki
H
Tanaka
Nobuho
N
Katsuragawa
Yozo
Y
Yamamoto
Seizo
S
Sawabe
Motoji
M
Juji
Takuo
T
Mori
Toshihito
T
Suzuki
Ryuji
R
Ikegawa
Shiro
S
D000368:Aged; D000369:Aged, 80 and over; D001842:Bone and Bones / Q000502:physiology; D002358:Cartilage, Articular / Q000473:pathology / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D045726:Metalloproteases / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D045726:Metalloproteases