Deficiency of tenascin-C delays articular cartilage repair in mice.
OBJECTIVE
In human articular cartilage, tenascin-C (TN-C) expression decreases during maturation of chondrocytes, and almost disappears in adults; however, it reappears in damaged cartilage. To examine the effects of TN-C on cartilage degeneration and repair, we compared articular cartilage degeneration between wild-type (WT) and tenascin-C knockout mouse (TNKO) mice using a spontaneous osteoarthritis (OA) in aged joints and surgical OA model. In addition, we made full-thickness cartilage defects and compared the cartilage repair process between the two groups.


METHODS
The surgical procedure to create degenerative OA model was performed by transecting the anterior cruciate ligament and medial collateral ligament. Full-thickness defects were created in the center of the femoral trochlea to evaluate cartilage repair. Sections of cartilage were stained with hematoxylin and eosin or safranin-O, and immunostaining for TN-C. The degrees of degeneration and repair were graded.


RESULTS
In the WT surgical OA model, the articular cartilage was almost normal at 2 weeks, but safranin-O decreased staining at 4 weeks. In TNKO mice, safranin-O decreased staining at 2 weeks, and cartilage was injured intensely at 4 weeks. In the cartilage repair model, TN-C was expressed after 1 week, was strongly expressed in the upper layer of regenerated tissue after 3 weeks, and disappeared after 6 weeks. The defects were restored until 6 weeks in WT mice; however, defects in TNKO mice were filled with fibrous tissue with no cartilage-like tissue.


CONCLUSIONS
This study revealed that cartilage repair in TNKO mice was significantly slower than that in WT mice and that the deficiency of TN-C progressed during cartilage degeneration.
Okamura
N
N
Departments of Orthopedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
Hasegawa
M
M
Nakoshi
Y
Y
Iino
T
T
Sudo
A
A
Imanaka-Yoshida
K
K
Yoshida
T
T
Uchida
A
A
D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D017888:Medial Collateral Ligament, Knee / Q000293:injuries; D051379:Mice; D018345:Mice, Knockout / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology*; D019063:Tenascin / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D019063:Tenascin