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LIGHT (TNFSF14) is a member of the TNF superfamily and is known to substitute for RANKL to induce osteoclast differentiation. LIGHT binds HVEM and LTβR, 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 LTβR; 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.

Original publication

DOI

10.1016/j.yexmp.2013.01.003

Type

Journal article

Journal

Experimental and molecular pathology

Publication Date

04/2013

Volume

94

Pages

380 - 385

Addresses

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford OX3 7HE, United Kingdom.

Keywords

Leukocytes, Mononuclear, Cells, Cultured, Osteoclasts, Stem Cells, Humans, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Antigens, CD14, Signal Transduction, Cell Differentiation, Proto-Oncogene Proteins c-akt, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Osteoprotegerin, Receptors, Tumor Necrosis Factor, Member 14, Lymphotoxin beta Receptor, Tumor Necrosis Factor Ligand Superfamily Member 14