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LIGHT acts as an osteoclastogenic and osteoblastogenic factor in mouse bone marrow cultures

Members of the TNF superfamily are involved in a broad range of biological functions such as cell proliferation, differentiation, and apoptosis, within the immune as well as within the bone system. The recently described TNF family member LIGHT (herpes virus entry mediator [HVEM]- L/TNFSF14) is expressed as a homotrimer on activated T cells and also on immature dendritic cells (Pfeffer, Cytokine Growth Factor Rev 2003). Three receptors with distinct cellular expression patterns on a variety of cell types are described to interact with LIGHT: lymphotoxin-beta receptor, HVEM, and DcR3 (TR6) lacking a transmembrane region, thereby acting as a negative regulator. In our study we investigated the role of LIGHT in the osteoclast formation from murine bone marrow cells. C57BL/6 (B6) mice and mice knock-out for LIGHT (LIGHT ko) (Scheu S et al, J Exp Med 2002) were used as a source of bone marrow cells. Osteoclasts were generated by the addition of rmM-CSF and rmRANKL (15 ng/mL for both) to the bone marrow cell cultures. In some experiments, different doses of rmLIGHT (10-80 ng/mL) were added in addition to M-CSF and RANKL. Osteoclast-like (OCL) cells were identified as tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells with three or more nuclei per cell, by light microscopy. The number of OCL cells were significantly lower in bone marrow cultures from LIGHT ko mice compared with cultures from B6 mice (244.3&#177; 3.6 vs. 274.1&#177; 4.7 respectively, p<0.05). Moreover, treatment of bone marrow cultures with LIGHT in doses of 40 and 80 ng/mL in addition to M-CSF and RANKL significantly increased the number of TRAP positive OCL cells (420.7&#177; 123.3 and 506.2&#177; 94.1 respectively) compared with cultures treated only with RANKL and M-CSF (279.3&#177; 59.0, p<0.05). Our preliminary results indicate that LIGHT has the role in the regulation of osteoclastogenesis from hematopoietic progenitors in the mouse bone marrow, in addition to its role within the immune system. Those findings also emphasize the functional relations between bone and immune systems, mediated by several members of the TNF superfamily.

LIGHT; osteoclast; osteoblast; bone marrow

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