LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease
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Giacomina Brunetti1,*, Rita Rizzi2,*, Angela Oranger1, Isabella Gigante1, Giorgio Mori3, Grazia Taurino1, Teresa Mongelli1, Graziana Colaianni1, Adriana Di Benedetto1, Roberto Tamma1, Giuseppe Ingravallo4, Anna Napoli4, Maria Felicia Faienza5, Anna Mestice2, Paola Curci2, Giorgina Specchia2, Silvia Colucci1,*, Maria Grano1,*
1Department of Basic and Medical Sciences, Neurosciences and Sense Organs, section of Human Anatomy and Histology, University of Bari, Bari, Italy
2Department of Emergency and Organ Transplantation, Section of Hematology with Transplantation, University of Bari, Bari, Italy
3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
4Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
5Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy
*These authors contributed equally to this work
Brunetti Giacomina, e-mail: [email protected]
Keywords: LIGHT/TNFSF14, multiple myeloma, bone disease, osteoclast, osteoblast
Received: August 08, 2014 Accepted: October 23, 2014 Published: November 12, 2014
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.
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