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.
Highlights
Multiple Myeloma (MM)-bone disease, characterized by osteolytic lesions, is the most frequent clinical manifestation of symptomatic MM, being detected in 70 to 80% of patients at diagnosis and up to 90% at relapse
LIGHT expression was detected in CD14+ monocytes from all the positive samples whereas, in 50% of them, it was detected in CD2+ T-cells and/or neutrophils, too
The results of the present study highlighted the high expression of LIGHT in peripheral blood (PB) and bone marrow (BM) samples from the large majority of MM-bone disease patients at diagnosis, in whom LIGHT was demonstrated to be involved in both increased osteoclastogenesis and decreased osteoblastogenesis
Summary
Multiple Myeloma (MM)-bone disease, characterized by osteolytic lesions, is the most frequent clinical manifestation of symptomatic MM, being detected in 70 to 80% of patients at diagnosis and up to 90% at relapse. Anti-LIGHT monoclonal antibody affects osteoclast formation in cultures of PBMCs and BMMNCs from MM-bone disease patients In culture media of PBMCs and BM mononuclear cells (BMMNCs) from MM-bone disease patients, we found higher LIGHT levels than in those from controls
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