ECTS2014 Poster Presentations Cell biology: osteoclasts and bone resorption (22 abstracts)
Involvement of LIGHT in multiple myeloma bone disease
Angela Oranger 1 , Giacomina Brunetti 1 , Giorgio Mori 2 , Claudia Carbone 1 , Isabella Gigante 1 , Teresa Mongelli 1 , Grazia Taurino 1 , Rita Rizzi 3 , Anna Mestice 1 , Alberta Zallone 1 , Giorgina Specchia 3 , Silvia Colucci 1 & Maria Grano 1
1Basic Medical Sciences, Neurosciences and Sense Organs, Bari, Italy; 2Clinical and Experimental Medicine, Foggia, Italy; 3Department of Emergency and Organ Transplantation, Bari, Italy.
Multiple myeloma (MM)-bone disease occurs in 70 to 80% of patients at MM diagnosis, and up to 90% at relapse; skeletal related events cause high morbidity and mortality. MM-bone disease consists of lytic lesions arising as a consequence of an unbalanced bone remodelling due to osteoclast (OC) activation, and osteoblast inactivation. Osteoclastogenesis may be under immune cell regulation through the production of numerous cytokines, such as LIGHT/TNFSF14, a newly identified member of the TNF superfamily, expressed by activated leukocytes. Recent literature data linked the high serum levels of LIGHT with the bone loss associated to rheumatoid arthritis. Thus, we investigated the role of LIGHT in MM-bone disease.
Interestingly, for the first time we demonstrated higher expression levels of LIGHT in T-cells, macrophages and polymorphonuclear cells from osteolytic MM patients respect to the same cells from asymptomatic MM patients as well as Monogammopathy of Undetermined Significant and healthy subjects. In particular, in osteolytic MM patients by flow cytometry we found high expression levels of LIGHT on CD8+ and CD4+CD25(high) T-cells, as well as on CD14+CD16+ monocytes, considered the principal source of OC precursors. We also demonstrated LIGHT expression in bone marrow biopsies from MM osteolytic patients. Moreover, to evaluate LIGHT involvement in MM bone disease, we investigated the effect of a LIGHT neutralizing antibody on bone cell differentiation in vitro. We found that the inhibition of the molecule significantly reduces OC formation from PBMCs of osteolytic MM patients, as well as stimulates OB differentiation in cultures derived from MM bone marrow mononuclear cells, as demonstrated by the increase of colony forming units of OBs and by the up-regulation of osterix transcription factor, bone sialoprotein and osteocalcin bone matrix proteins. In conclusion, our data demonstrated LIGHT involvement in MM bone disease and suggest it as new potential therapeutic target for MM management.
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Bone Abstracts
ISSN 2052-1219 (online)
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