NDLI: LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease.

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LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease.

Content Provider	Europe PMC
Author	Brunetti, Giacomina Rizzi, Rita Oranger, Angela Gigante, Isabella Mori, Giorgio Taurino, Grazia Mongelli, Teresa Colaianni, Graziana Di Benedetto, Adriana Tamma, Roberto Ingravallo, Giuseppe Napoli, Anna Faienza, Maria Felicia Mestice, Anna Curci, Paola Specchia, Giorgina Colucci, Silvia Grano, Maria
Copyright Year	2014
Abstract	LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease associated with rheumatoid arthritis. Herein, we investigated whether LIGHT has a role in Multiple Myeloma (MM)-bone disease. We found that LIGHT was overproduced by CD14+ monocytes, CD8+ T-cells and neutrophils of peripheral blood and bone marrow (BM) from MM-bone disease patients. We also found that LIGHT induced osteoclastogenesis and inhibited osteoblastogenesis. In cultures from healthy-donors, LIGHT induced osteoclastogenesis in RANKL-dependent and -independent manners. In the presence of a sub-optimal RANKL concentration, LIGHT and RANKL synergically stimulated osteoclast formation, through the phosphorylation of Akt, NFκB and JNK pathways. In cultures of BM samples from patients with bone disease, LIGHT inhibited the formation of CFU-F and CFU-OB as well as the expression of osteoblastic markers including collagen-I, osteocalcin and bone sialoprotein-II. LIGHT indirectly inhibited osteoblastogenesis in part through sclerostin expressed by monocytes. In conclusion, our findings for the first time provide evidence for a role of LIGHT in MM-bone disease development.
Journal	Oncotarget
Volume Number	5
PubMed Central reference number	PMC4350341
Issue Number	24
PubMed reference number	25460501
e-ISSN	19492553
DOI	10.18632/oncotarget.2633
Language	English
Publisher	Impact Journals LLC
Publisher Date	2014-12-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Copyright: © 2014 Brunetti et al.
Subject Keyword	LIGHT/TNFSF14 multiple myeloma bone disease osteoclast osteoblast
Content Type	Text
Resource Type	Article
Subject	Oncology

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