Expression of collagen and aggrecan genes in normal and osteoarthritic murine knee joints.
OBJECTIVE
The STR/ort mouse strain develops osteoarthritis (OA) of the medial tibial cartilage whilst CBA mice do not develop this disease. We investigated whether changes occur in the expression of genes encoding major extracellular matrix proteins in the connective tissue of the murine knee joint in OA.


METHODS
Expression of the genes encoding collagens II (Col2alpha1), X (Col10alpha1), alpha2(XI) (Col11alpha2) and aggrecan (Agc) was detected in skeletally mature and immature male mice of the CBA and STR/ort strains by in situ hybridization.


RESULTS
Col2alpha1 was expressed by chondrocytes of the tibial and patella-femoral cartilage and by the meniscal cartilage in all young mice (4-9 weeks) but only in the patella-femoral cartilage in older mice of both strains (36-45 weeks). In contrast Col2alpha1 was expressed by growth plate chondrocytes of both species at all ages. Similarly, Col2alpha1 transcripts were detected in cruciate ligament cells in both strains at all ages. Col10alpha1 transcripts were detected in cruciate ligament cells in both strains at all ages. Col10alpha1 expression was evident in the hypertrophic chondrocytes in the growth plate of young CBA and STR mice, but was not active in these cells in mature animals. However, Col10alpha1 was transcribed in articular chondrocytes of the tibia, meniscal and patella-femoral cartilages of all ages, in normal and osteoarthritic mice. Transcripts were also present in ligament of some mature animals. Col11alpha2 followed a similar pattern of expression in CBA cartilages to Col2alpha1, being active in adult growth plate but generally inactive in adult articular cartilages. Young CBA and STR/ort mice expressed Col11alpha2 in articular cartilage and very strongly throughout the growth plate. Agc expression was detected in all articular cartilages at all ages in both strains. Interestingly, transcripts for all four genes were absent in tibial articular chondrocytes located close to osteoarthritic lesions in STR/ort mice, indicating that these cells are unable to synthesize matrix proteins. Adult STR/ort mice also showed evidence of tissue remodeling around the periphery of the knee joint. Cells in remodeling areas actively transcribed Col2alpha1, Col10alpha1, Col11alpha2 and Agc.


CONCLUSIONS
It is unlikely that OA develops in STR/ort mice because of failure to express major proteins in joint tissue. However, once lesions develop in articular cartilage neighbouring chondrocytes fail to express genes encoding several matrix proteins.
Chambers
M G
MG
Cell & Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, London, England.
Kuffner
T
T
Cowan
S K
SK
Cheah
K S E
KS
Mason
R M
RM
D053674:Aggrecans; D000375:Aging / Q000502:physiology; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D024161:Collagen Type XI / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D015870:Gene Expression; D017403:In Situ Hybridization; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*
C508320:Acan protein, mouse; D053674:Aggrecans; D024043:Collagen Type II; D024121:Collagen Type X; D024161:Collagen Type XI; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D003094:Collagen