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AB0055 (2023)
THE ROLES OF OX40L AND TNF BISPECIFIC ANTIBODY IN OSTEOCLASTOGENESIS
H. S. Kwon1, J. Y. Kim2, S. U. Kim2, J. S. Lee3, H. R. Kang4,5, S. Ban1, E. Y. Lee2
1Seoul National University, Department of Cancer Biology, Seoul, Korea, Rep. of (South Korea)
2Seoul National University Hospital, Division of Rheumatology, Department of Internal Medicine, Seoul, Korea, Rep. of (South Korea)
3Korea Advanced Institute of Science and Technology, Graduate School of Medical Science and Engineering, Daejeon, Korea, Rep. of (South Korea)
4Seoul National University, Interdisciplinary Program in Cancer Biology, Seoul, Korea, Rep. of (South Korea)
5Seoul National University, Integrated Major in Innovative Medical Science, Seoul, Korea, Rep. of (South Korea)

 

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.

Figure 1.

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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.

Keywords: Osteoarthritis, Rheumatoid arthritis, Adaptive immunity

DOI: 10.1136/annrheumdis-2023-eular.5450

Citation: , volume 82, supplement 1, year 2023, page 1206
Session: Rheumatoid arthritis - aetiology, pathogenesis and animal models (Publication only)