Session Type: Poster Session D
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction. Filgotinib is a selective small molecule inhibitor of JAK 1 enzymes, and is currently in clinical development for the treatment of rheumatoid arthritis (RA). However, a direct role of filgotinib for osteogenesis has not been demonstrated. Here, we examined filgotinib inhibited monocyte differentiation and proinflammatoly cytokine production in osteoblasts.
Methods: To determine if the JAK-STAT enzyme was expressed in RA osteoblasts and MG63 (human osteosarcoma cell line), we performed immunohistochemistry. In order to confirm that filgotinib inhibited STAT signaling phosphorylation, interleukin (IL)-6 and IL-6 receptor (IL-6R) stimulated MG63 was used for western blotting. To determine whether filgotinib was involved in proinflammatoly cytokine production, monocyte chemotactic protein-1(MCP-1)/CCL2, IL-8/CXCL8, receptor activator for nuclear factor -κB ligand (RANKL) and CXCL16 in filgotinib treated MG63 conditioned medium was measured using enzyme-linked immunosorbent assay (ELISA). Finally, to confirm if monocyte was differentiated with filgotinib, THP-1 (human acute monocytic leukemia cell line) was cultured with filgotinib treated MG63 conditioned medium.
Results: JAK1, 2 and 3 was expressed in osteoblast and MG63. We found that phosphorylated STAT1 and STAT3 signaling in IL-6 and IL-6R stimulated filgotinib treated MG63 was significantly decreased at 10 minutes compared to nontreated MG63. MCP-1/CCL2 in filgotinib treated MG63 conditioned medium was significantly decreased compared with in nontreated MG63 conditioned medium (12.8 ± 0.6 pg/ml and 41.6 ± 0.0 pg/ml, p< 0.05, respectively). CXCL16 in in filgotinib treated MG63 conditioned medium was also significantly decreased compared with in nontreated MG63 conditioned medium (12.8 ± 0.6 pg/ml and 41.6 ± 0.0 pg/ml, p< 0.05, respectively). Additionally, THP-1 with IL-6 and IL-6R treated MG63 conditioned medium differentiated into multinuclear cells. On the other hand, THP-1 with filgotinib treated MG63 conditioned medium did not differentiate into multinuclear cells.
Conclusion: Filgotinib inhibited proinflammatory cytokine production and monocyte differentiation. These data indicate that filgotinib acts on bone metabolism, suggesting that filgotinib may prevent bone destruction.
To cite this abstract in AMA style:Isozaki T, Ikari Y, Kasama T. Filgotinib Inhibits Monocyte Differentiation and Pro Inflammatoly Cytokine Production in Osteoblasts [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/filgotinib-inhibits-monocyte-differentiation-and-pro-inflammatoly-cytokine-production-in-osteoblasts/. Accessed August 3, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/filgotinib-inhibits-monocyte-differentiation-and-pro-inflammatoly-cytokine-production-in-osteoblasts/