Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in Chondrocytes
International Journal of Oral Biology
;
: 9-15, 2016.
Article
in English
| WPRIM
| ID: wpr-32084
ABSTRACT
Receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell-derived essential factor for osteoclastogenesis. During endochondral bone formation, hypertrophic chondrocytes calcify cartilage matrix that is subsequently resorbed by osteoclasts in order to be replaced by new bone. Hypoxia-induced upregulation of RANKL expression has been previously demonstrated in an in vitro system using osteoblasts; however, the involved mechanism remains unclear in chondrocytes. In the present study, we investigated whether hypoxia regulates RANKL expression in ATDC5 cells, a murine chondrogenic cell line, and hypoxia-inducible factor-1α (HIF-1α) mediates hypoxia-induced RANKL expression by transactivating the RANKL promoter. The expression levels of RANKL mRNA and protein, as well as HIF-1α protein, were significantly increased in ATDC5 cells under hypoxic condition. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression under normoxic conditions, whereas dominant negative HIF-1α reduced hypoxia-induced RANKL expression. HIF-1α increased RANKL promoter reporter activity in a HIF-1α binding element-dependent manner in ATDC5 cells. Hypoxia-induced RANKL levels were much higher in differentiated ATDC5 cells, as compared to proliferating ATDC5 cells. These results suggested that under hypoxic conditions, HIF-1α mediates induction of RANKL expression in chondrocytes; in addition, hypoxia plays a role in osteoclastogenesis during endochondral bone formation, at least in part, through the induction of RANKL expression in hypertrophic chondrocytes.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Osteoblasts
/
Osteoclasts
/
Osteogenesis
/
RNA, Messenger
/
Cartilage
/
Up-Regulation
/
Cell Line
/
Chondrocytes
/
RANK Ligand
/
Hypoxia
Language:
English
Journal:
International Journal of Oral Biology
Year:
2016
Type:
Article
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