More knee joint osteoarthritis (OA) in mice after inactivation of one allele of type II procollagen gene but less OA after lifelong voluntary wheel running exercise.
OBJECTIVE
To investigate the incidence and severity of osteoarthritis (OA) and the effects of voluntary wheel running in normal mice and mice carrying either a targeted inactivation of one allele, heterozygous 'knockout', of Col2a1 gene or both alleles, homozygous 'knockout', of Col11a2 gene.


METHODS
Mice lived until 15 months of age in individual cages. Running activity was recorded around the clock. OA changes were evaluated from serial knee joint sections by light microscopy.


RESULTS
Heterozygous inactivation of Col2a1 gene coding for type II procollagen made the cartilage more susceptible to OA. At 15 months of age, OA prevalence was 60-90% in knockouts and 20-45% in normal controls (P < 0.01-0.001). Unexpectedly, a reduction of OA due to wheel running was observed in both knockout strains (P< 0.05-0.01). This effect was most evident in the femoral condyles. Incidence of OA in runners was approximately 50-85% of that in sedentary littermates. OA prevalence was higher in normal control and runner mice with high body weight. Running did not affect OA development in normal mice.


CONCLUSIONS
Heterozygous knockout of Col2a1 gene increased the OA prevalence in mice. Lifelong voluntary wheel running had a protective effect against OA in both knockout mice lines. The reason for this remains unknown. Reduction of OA may result from the reorganization and strengthening of the articular cartilage collagen network and/or adjacent muscles due to running, or lower body weight. Increased compliance of the articular cartilage and bones of the knockout mice may also contribute to the reduction of OA in exercised animals.
Lapveteläinen
T
T
Department of Anatomy, University of Kuopio, Kuopio, 70211, Finland.
Hyttinen
M
M
Lindblom
J
J
Långsjö
T K
TK
Sironen
R
R
Li
S W
SW
Arita
M
M
Prockop
D J
DJ
Puustjärvi
K
K
Helminen
H J
HJ
D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002358:Cartilage, Articular / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000209:etiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011347:Procollagen / Q000172:deficiency*
D011347:Procollagen