AB0055 THE ROLES OF OX40L AND TNF BISPECIFIC ANTIBODY IN OSTEOCLASTOGENESIS

Background

Rheumatoid arthritis (RA) is a chronic, inflammatory disease that leads to progressive cartilage and bone destruction. OX40 ligand (OX40L) is expressed predominantly on antigen-presenting cells and highly associated with joint inflammation in RA^[1]. Yet, the role of OX40L in osteoclastogenesis is unclear.

Objectives

In this study, we investigated the effects of dual blocking of TNF and OX40L by bispecific antibody (IMB-101) on RANKL-induced osteoclastogenesis.

Methods

CD14+ monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of healthy donors (n=6). CD14+ monocytes were cultured with M-CSF (20ng/ml) and RANKL (40ng/ml) for 6 to 7 days in the presence of TNF antibody, OX40L antibody, or bispecific antibody. TRAP-positive multinucleated giant cells (>3 nuclei/cell) were counted as osteoclast. PU.1, RANK and NFATc1, markers of osteoclast differentiation were assessed by the quantitative reverse transcription PCR (RT-qPCR). The expression of OX40L was analyzed in the presence of RANKL or TNF at the early and late stage of osteoclast differentiation.

Results

The expression of OX40L was increased by RANKL and TNF at the early stage of osteoclast differentiation (day 3) in a TNF dose-dependent manner. IMB-101 decreased RANKL-induced osteoclastogenesis via downregulating NFATc1 expression (Figure 1). IMB-101 further reduced PU.1, RANK and NFATc1 expression during early stage of osteoclast differentiation (day 3) compared to TNF inhibitor or TNF inhibitor and OX40L inhibitor (n=3).

Conclusion

Our data suggested that IMB-101 might have a beneficial effect on imbalance of the bone resorption in RA especially by suppressing osteoclast differentiation.

Reference

[1]Yoshioka, Taro et al. "Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis." European Journal of Immunology 30 (2000): n. pag.

Acknowledgements:

NIL.

Disclosure of Interests

None Declared.