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

// Giacomina Brunetti 1, * , Rita Rizzi 2, * , Angela Oranger 1 , Isabella Gigante 1 , Giorgio Mori 3 , Grazia Taurino 1 , Teresa Mongelli 1 , Graziana Colaianni 1 , Adriana Di Benedetto 1 , Roberto Tamma 1 , Giuseppe Ingravallo 4 , Anna Napoli 4 , Maria Felicia Faienza 5 , Anna Mestice 2 , Paola Curci 2 , Giorgina Specchia 2 , Silvia Colucci 1, * , Maria Grano 1, * 1 Department of Basic and Medical Sciences, Neurosciences and Sense Organs, section of Human Anatomy and Histology, University of Bari, Bari, Italy 2 Department of Emergency and Organ Transplantation, Section of Hematology with Transplantation, University of Bari, Bari, Italy 3 Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy 4 Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy 5 Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy * These authors contributed equally to this work Correspondence to: Brunetti Giacomina, e-mail: giacomina.brunetti@uniba.it Keywords: LIGHT/TNFSF14, multiple myeloma, bone disease, osteoclast, osteoblast Received: August 08, 2014      Accepted: October 23, 2014      Published: November 12, 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.