Immobilization-induced cartilage degeneration mediated through expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and chondromodulin-I.
Immobilization results in thinning of the articular cartilage and cartilage degeneration, although the exact mechanisms are not clear yet. Hypoxia is thought to contribute to the degeneration of articular cartilage. We investigated the roles of hypoxia inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), and the newly cloned antiangiogenic factor, chondromodulin-I (ChM-1), in cartilage degeneration in immobilized joints. Male Wistar rats (n = 30, 12-week-old) were divided randomly into the control group (n = 10), immobilization group (n = 10), and continuous passive motion (CPM) group (n = 10). In the immobilization group, the ankle joints were fixed in full plantar flexion with plaster casts for 4 weeks. In the CPM group, the ankle casts were removed during the immobilization period and the ankle joints were subjected to CPM. Significant thinning of the articular cartilage was noted in the immobilization group but not in the control or CPM group. In the immobilized group, vascular channels were found in the area between the calcified cartilage zone and the subchondral bone. The densities of HIF-1alpha-and VEGF-immunostained cells were higher in the immobilized group than the other two groups. In contrast, low expression of ChM-1 was detected in the articular cartilage of the immobilized group compared with the control and CPM group. Our results showed that immobilization induces thinning of the articular cartilage and appearance of vascular channel, in areas with balanced expression of HIF-1alpha/VEGF and ChM-1.
Sakamoto
Junya
J
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Origuchi
Tomoki
T
Okita
Minoru
M
Nakano
Jiro
J
Kato
Katsutomo
K
Yoshimura
Toshiro
T
Izumi
Shin-ichi
S
Komori
Toshihisa
T
Nakamura
Hideki
H
Ida
Hiroaki
H
Kawakami
Atsushi
A
Eguchi
Katsumi
K
D000704:Analysis of Variance; D000818:Animals; D002357:Cartilage Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007103:Immobilization / Q000009:adverse effects*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013643:Tarsus, Animal / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C489407:Cnmd protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A