Document Detail

HIF-2α as a possible therapeutic target of osteoarthritis.
MedLine Citation:
PMID:  20950696     Owner:  NLM     Status:  In-Process    
OBJECTIVE: Endochondral ossification, a conversion process from nonvascularized and hypoxic cartilage to highly vascularized bone, plays a crucial role in osteoarthritis (OA) development as well as in physiological skeletal growth. We have shown that hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is an extensive regulator of the endochondal ossification process. Here we review the possible signaling network regulating OA development on the axis of HIF-2α.
METHODS: Peer reviewed publications published prior to August 2010 were searched in the Pubmed database. Articles that were relevant to HIF and molecular mechanisms of the endochondral ossification and OA were selected.
RESULTS: As a trigger of OA, mechanical stress may induce the upstream NF-κB signal and HIF-2α expression in joint cartilage of mice and humans, which causes transactivation of endochondral ossification-related molecules with the most potent β-subunit partner aryl hydrocarbon nuclear translocator-like (ARNTL). In contrast to HIF-2α, HIF-1α functions to maintain cartilage via a distinct mechanism, so that the shifting of the HIFs might possibly be involved in an OA pathogenesis.
CONCLUSION: Signals on the HIF-2α axis from NF-κB signaling to the endochondral ossification-related molecules, possibly in combination with HIF-2α and ARNTL, may represent a rational therapeutic target for OA with minimal effects on physiological skeletal homeostasis.
T Saito; H Kawaguchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-13
Journal Detail:
Title:  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society     Volume:  18     ISSN:  1522-9653     ISO Abbreviation:  Osteoarthr. Cartil.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9305697     Medline TA:  Osteoarthritis Cartilage     Country:  England    
Other Details:
Languages:  eng     Pagination:  1552-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Bone & Cartilage Regenerative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
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