Roles of hypoxia inducible factor-1α in the temporomandibular joint.
OBJECTIVE
Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease characterized by permanent cartilage loss. Articular cartilage is maintained in a low-oxygen environment. The chondrocyte response to hypoxic conditions involves expression of hypoxia inducible factor 1α (HIF-1α), which induces chondrocytes to increase expression of vascular endothelial growth factor (VEGF). Here, we investigated the role of HIF-1α in mechanical load effects on condylar cartilage and subchondral bone in heterozygous HIF-1α-deficient mice (HIF-1α+/-).


METHODS
Mechanical stress was applied to the TMJ of C57BL/6NCr wild-type (WT) and HIF-1α+/-mice with a sliding plate for 10 days. Histological analysis was performed by HE staining, Safranin-O/Fast green staining, and immunostaining specific for articular cartilage homeostasis.


RESULTS
HIF-1α+/-mice had thinner cartilage and smaller areas of proteoglycan than WT controls, without and with mechanical stress. Mechanical stress resulted in prominent degenerative changes with increased expression of HIF-1α, VEGF, and the apoptosis factor cleaved Caspase-3 in condylar cartilage.


CONCLUSIONS
Our results indicate that HIF-1α may be important for articular cartilage homeostasis and protective against articular cartilage degradation in the TMJ under mechanical stress condition, therefore HIF-1α could be an important new therapeutic target in TMJ-OA.
Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Akiko
A
Mino-Oka
Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Takashi
T
Izawa
Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Takehiro
T
Shinohara
Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Hiroki
H
Mori
Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Akihiro
A
Yasue
Department of Pharmacology, Osaka City University, Faculty of Medicine, Osaka, Japan.
Shuhei
S
Tomita
Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan; Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: etanaka@tokushima-u.ac.jp.
Eiji
E
Tanaka
D000818:Animals; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D019902:Chondrocytes / Q000502:physiology; D006579:Heterozygote; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008334:Mandible / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010100:Oxygen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013314:Stress, Mechanical; D013704:Temporomandibular Joint / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D051033:Apoptosis Inducing Factor; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D010100:Oxygen
Articular cartilage degradation; Chondrocyte apoptosis; Hypoxia inducible factor-1α; Temporomandibular joint osteoarthritis (TMJ-OA)