TY - JOUR
T1 - Roles of hypoxia inducible factor-1α in the temporomandibular joint
AU - Mino-Oka, Akiko
AU - Izawa, Takashi
AU - Shinohara, Takehiro
AU - Mori, Hiroki
AU - Yasue, Akihiro
AU - Tomita, Shuhei
AU - Tanaka, Eiji
N1 - Funding Information:
This study was supported by Grants-in-Aid 26293436 (E.T.), 21792078 (A.Y.), 25713063 (T.I.) and 15K15757 (T.I.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan . The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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+/−). Design 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. Conclusion 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.
AB - 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+/−). Design 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. Conclusion 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.
KW - Articular cartilage degradation
KW - Chondrocyte apoptosis
KW - Hypoxia inducible factor-1α
KW - Temporomandibular joint osteoarthritis (TMJ-OA)
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U2 - 10.1016/j.archoralbio.2016.10.028
DO - 10.1016/j.archoralbio.2016.10.028
M3 - Article
C2 - 27816790
AN - SCOPUS:84994653099
SN - 0003-9969
VL - 73
SP - 274
EP - 281
JO - Archives of Oral Biology
JF - Archives of Oral Biology
ER -