Investigation of osteoclastogenic signalling of the RANKL substitute LIGHT.
Exp Mol Pathol
; 94(2): 380-5, 2013 Apr.
Article
in En
| MEDLINE
| ID: mdl-23391709
ABSTRACT
LIGHT (TNFSF14) is a member of the TNF superfamily and is known to substitute for RANKL to induce osteoclast differentiation. LIGHT binds HVEM and LTßR, but it is not known whether these receptors play a role in osteoclast formation or whether LIGHT acts via RANKL signalling pathways. We found that both RANKL and LIGHT strongly induced phosphorylation of Akt and NFκB but not JNK in mouse osteoclast precursor cells. The addition of an Akt inhibitor showed decreased osteoclast differentiation and resorption mediated by both RANKL and LIGHT. RT-PCR and FACS analysis showed that CD14(+) human osteoclast precursors expressed HVEM and LTßR; expression levels of HVEM increased in the course of osteoclastogenesis and a decrease in LIGHT expression was associated with an increase in HVEM suggesting that there is a feedback loop related to this receptor. Our findings show that LIGHT is not inhibited by the soluble RANKL receptor OPG and that LIGHT is a potent osteoclastogenesis factor that activates the Akt, NFκB and JNK pathways.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoclasts
/
Tumor Necrosis Factor Ligand Superfamily Member 14
/
Lymphotoxin beta Receptor
/
Receptors, Tumor Necrosis Factor, Member 14
/
Osteoprotegerin
Limits:
Humans
Language:
En
Journal:
Exp Mol Pathol
Year:
2013
Document type:
Article
Affiliation country:
United kingdom
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS