THE ROLE OF LIGHT ON BONE REMODELING

LIGHT, expressed by different cells of the immune system, binds two trans-membrane receptors: HVEM and LT?R. It is over-expressed in erosive rheumatoid arthritis and lytic myeloma-bone disease and controversial data have been published on its role in vitro osteoclast (OC) formation. Here, we investigated the role of LIGHT on in vitro murine osteoclastogenesis model and bone phenotype in LIGHT-/- mice. Firstly, we showed that murine macrophages stimulated with LIGHT alone did not differentiate into OCs. Consistently, the addition of agonist anti-HVEM and anti-LT?R antibodies did not affect osteoclastogenesis in the same cultures. Interestingly, the presence of LIGHT and sub-optimal RANKL concentration displayed synergic effects on OC formation through the early and sustained activation of Akt, NF?B and JNK pathways. Secondly, by microCT we found that the femurs of LIGHT-/- mice exhibited a decrease in trabecular BV/TV due to a significant reduction in trabecular thickness and number as well as the increase in trabecular spaces respect to wild-type (WT) mice. Further, a deformity of the vertebral column due to the collapse of vertebral bodies was radiographically observed in about 40% of LIGHT-/- mice. To investigate the possible molecular mechanism/s responsible for this bone phenotype in LIGHT-/- mice we studied OPG levels in whole bone marrow extracts from the femurs of these mice and demonstrated a significant reduction in OPG mRNA transcript respect to WT. Based on the knowledge that mature B cells are the major source of OPG and that they represent about 50% of the spleen cells, we treated with LIGHT total splenocytes demonstrating a three fold increase of OPG mRNA levels respect to the untreated cells. In conclusion, our results suggested that the net effect of LIGHT on bone remodeling probably occurs through the modulation of OPG expression. However, further experiments are needed to better clarify this issue