Analysis of early changes in the articular cartilage transcriptisome in the rat meniscal tear model of osteoarthritis: pathway comparisons with the rat anterior cruciate transection model and with human osteoarthritic cartilage.
OBJECTIVE
The purpose of this study was to use microarray technology to: (1) understand the early molecular events underlying the damage of articular cartilage initiated by this surgical procedure, and (2) determine whether these changes mimic those that are occurring in human osteoarthritic (OA) cartilage.


METHODS
Cartilage was harvested from both medial and lateral sides of the tibial plateaus and femoral condyles of both meniscal tear (MT) and sham surgery groups on days 3, 7 and 21 post-surgery. mRNA prepared from these rat cartilage samples was used for microarray analysis.


RESULTS
Statistical analysis identified 475 genes that were differentially expressed between the sham and MT groups, at one or more of the time points that were analyzed. By integrating these genes with OA-related genes reported previously in a rat OA model and in human OA array studies, we identified 20 commonly changed genes. Six out of these 20 genes (Col5A1, Col6A2, INHBA, LTBP2, NBL1 and SERPINA1) were differentially expressed in two animal models and in human OA. Pathway analysis identified some key features of OA pathology, namely cartilage extracellular matrix remodeling, angiogenesis, and chondrocyte cell death that were recapitulated in the animal models. The rat models suggested increased inflammation and cholesterol metabolic pathways may play important role in early cartilage degeneration.


CONCLUSIONS
We identified a large number of differentially expressed genes in the articular cartilage of the MT model. While there was lack of overall identity in cartilage gene expression between the rat models and human OA, several key biological processes were recapitulated in the rat MT OA model.
Wei
T
T
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Kulkarni
N H
NH
Zeng
Q Q
QQ
Helvering
L M
LM
Lin
X
X
Lawrence
F
F
Hale
L
L
Chambers
M G
MG
Lin
C
C
Harvey
A
A
Ma
Y L
YL
Cain
R L
RL
Oskins
J
J
Carozza
M A
MA
Edmondson
D D
DD
Hu
T
T
Miles
R R
RR
Ryan
T P
TP
Onyia
J E
JE
Mitchell
P G
PG
D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D001169:Arthritis, Experimental / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D005269:Femur / Q000378:metabolism; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D023421:Models, Animal; D010003:Osteoarthritis / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013977:Tibia / Q000378:metabolism; D000070600:Tibial Meniscus Injuries