Regional differences in chondrocyte metabolism in osteoarthritis: a detailed analysis by laser capture microdissection.
OBJECTIVE
To determine the change in metabolic activity of chondrocytes in osteoarthritic (OA) cartilage, considering regional difference and degree of cartilage degeneration.


METHODS
OA cartilage was obtained from knee joints with end-stage OA, at both macroscopically intact areas and areas with various degrees of cartilage degeneration. Control cartilage was obtained from age-matched donors. Using laser capture microdissection, cartilage samples were separated into superficial, middle, and deep zones, and gene expression was compared quantitatively in the respective zones between OA and control cartilage.


RESULTS
In OA cartilage, gene expression changed markedly with the site. The expression of cartilage matrix genes was highly enhanced in macroscopically intact areas, but the enhancement was less obvious in the degenerated areas, especially in the upper regions. In contrast, in those regions, the expression of type III collagen and fibronectin was most enhanced, suggesting that chondrocytes underwent a phenotypic change there. Within OA cartilage, the expression of cartilage matrix genes was significantly correlated with SOX9 expression, but not with SOX5 or SOX6 expression. In OA cartilage, the strongest correlation was observed between the expression of type III collagen and fibronectin, suggesting the presence of a certain link(s) between their expression.


CONCLUSIONS
The results of this study revealed a comprehensive view of the metabolic change of the chondrocytes in OA cartilage. The change of gene expression profile was most obvious in the upper region of the degenerated cartilage. The altered gene expression at that region may be responsible for the loss of cartilage matrix associated with OA.
Fukui
Naoshi
N
National Hospital Organization Sagamihara Hospital, Sagamihara, Japan. n-fukui@sagamihara-hosp.gr.jp
Ikeda
Yasuko
Y
Ohnuki
Toshiyuki
T
Tanaka
Nobuho
N
Hikita
Atsuhiko
A
Mitomi
Hiroyuki
H
Mori
Toshihito
T
Juji
Takuo
T
Katsuragawa
Yozo
Y
Yamamoto
Seizo
S
Sawabe
Motoji
M
Yamane
Shoji
S
Suzuki
Ryuji
R
Sandell
Linda J
LJ
Ochi
Takahiro
T
D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D024061:Collagen Type III / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005109:Extracellular Matrix / Q000502:physiology*; D020869:Gene Expression Profiling; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D007834:Lasers; D042282:Microdissection; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D009810:Odontoma / Q000235:genetics; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
D024061:Collagen Type III; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; C490301:SOX5 protein, human; C486270:SOX6 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055755:SOXD Transcription Factors; D014157:Transcription Factors