Potential contribution of immature myeloid CD11c+dendritic cells-derived osteoclast precursor to inflammation-induced bone loss in the TRAF6-null chimeras in-vivo

Yen Chun G Liu; Andy Yen-Tung Teng

doi:10.1016/j.jds.2023.03.016

Potential contribution of immature myeloid CD11c⁺dendritic cells-derived osteoclast precursor to inflammation-induced bone loss in the TRAF6-null chimeras in-vivo

J Dent Sci. 2023 Jul;18(3):1372-1377. doi: 10.1016/j.jds.2023.03.016. Epub 2023 Apr 5.

Authors

Yen Chun G Liu¹, Andy Yen-Tung Teng^{2

3}

Affiliations

¹ Center for Osteo-immunology & Biotechnology Research (COBR) and Department of Dental Hygiene, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
² Center for Osteo-immunology & Biotechnology Research (COBR), School of Dentistry, College of Dental Medicine, Kaohsiung Medical University (KMU) and KMU-Hospital, Kaohsiung City, Taiwan.
³ Lab of Molecular Microbial Immunity and Div. of Periodontology, The Eastman Institute for Oral Health (EIOH), School of Medicine & Dentistry, University of Rochester, Rochester, NY, USA.

Abstract

Dendritic cells (DC) are potent antigen-presenting-cells widely distributed at the osteo-immune and/or mucosal-mesenchyme interface, consequentially implicating in certain bone-sparing disorders; i.e., via signaling Receptor-activator-of-nuclear-factor-kappa-B-ligand/RANKL-Receptor-activator-of-nuclear-factor-kB/RANK-Osteoprotegerin/OPG-TRAF6 transducer-complex etc., evidently associated with arthritis, osteoporosis and periodontitis. We have reported that the immature myeloid CD11c⁺-DC subsets can act as osteoclast precursor (OCp; mDDOCp), thereby developing into osteoclasts (OCs) via an alternative pathway for osteoclastogenesis. Importantly, cytokine TGF-β remains critical to prime CD11c⁺-mDDOCp-cells deficient of TRAF6-&-related immune/osteotropic signaling, featuring distinctive TGF-β-&-IL-17-invoked effectors in the environmental milieu sufficient to driving bona-fide osteoclastogenesis in-vitro. Herein, we sought to explore the potential contribution of immature-mDDOCp/OCp to inflammation-induced bone-loss, where comparable CD11c⁺TRAP⁺multinucleated-OC-like/mDDOCp existed, lacking the endogenous TRAF6-associated monocyte/macrophage-derived OCs in type-II-collagen induced joint/paw inflammation of the C56BL/6-TRAF6^(-/-)null chimeras (H-2^b-halpotype) examined. The results suggest that such TRAF6-null chimeric mice may offer a useful model to assess the specific functions of OCp or mDDOCp as an analog to human conditions in-vivo.

Keywords: Dendritic cells (DCs) & myeloid dendritic cell-derived osteoclast precursors (mDDOCp); Immune-osteotropic cytokines; Inflammation-induced bone loss; Osteoclast & osteoclastogenesis; TRAF6 & TGF-β signaling.