IADR Abstract Archives
Immature CD11c+/TRAF6(-/-)Myeloid-Dendritic-Cell-Derived Osteoclast-Precursor (MDDOCp) is Involved in Cytokines-Mediated Inflammatory Bone-Loss
Objectives: Inflammation-induced bone loss, a cardinal feature associated with the chronic musculoskeletal illnesses (i.e., arthritis, periodontitis, etc.), involves the critical RANKL/RANK-OPG-triad via TRAF6/adaptor- complex leading to regulatory-vs.-pathogenic sequelae at the osteo-immune interface, which remains unclear at present; for example, how and why do the multiple lineages (i.e., dendritic-cells-monocytes/macrophages-osteoclasts: DC-Mo/MΦ-OC) develop and then interact during subsequent pathogenesis awaits further study for better understanding.
Methods: We have established protocols to dissect how signaling interplays between TRAF6-adaptor and critical cytokines responsible for modulating osteoclastogenesis or/and bone remodeling, where various in-vitro/in-vivo approaches (e.g., gene knockout/siRNA-knockdown, Ab-neutralization, adoptive-transfer & bone-marrow-chimeras, etc.) were embarked to address: i) the developmental features of immature CD11c+/myeloid-DCs, as compared to the classical Mo/MΦ subsets, to the alternative pathway of osteoclastogenesis, ii) how signal interactions of key osteotropic cytokines (TGF-β, IL-17, etc.) with/without TRAF6/adaptor-complex in the environmental milieu may affect the bone remodeling underway (by the Student-t-test & ANOVA).
Results: The results showed that: i) immature CD11c+/myeloid-DC-derived-OC-precursors/mDDOCp are significantly involved with inflammation-induced bone loss, independent of the classical Mo/MΦ-derived-OCs in the TRAF6-KO chimeras; ii) IL-17 may engage a distinctive interplay with mDDOCp before developing to CD11c+TRAF6(-/-)DDOC via TGF-β-modulated step-wise pathway to arthritic bone loss in-vivo.
Conclusions: These findings suggest that this non-discriminative signaling via TGFβ-&-IL-17 for effector-activity in CD11c+/TRAF6(-/-)mDDOCp revealed herein may underpin a new insight for the alternative osteoclastogenesis, which will require further study for its in-vivo significance; i.e., arthritic & periodontal diseases. Such proposed twist-in-turns of osteo-immune interactions involving the classical-vs.-alternative pathways for inflammation-induced bone loss will be theme-highlighted in this presentation as well.
Methods: We have established protocols to dissect how signaling interplays between TRAF6-adaptor and critical cytokines responsible for modulating osteoclastogenesis or/and bone remodeling, where various in-vitro/in-vivo approaches (e.g., gene knockout/siRNA-knockdown, Ab-neutralization, adoptive-transfer & bone-marrow-chimeras, etc.) were embarked to address: i) the developmental features of immature CD11c+/myeloid-DCs, as compared to the classical Mo/MΦ subsets, to the alternative pathway of osteoclastogenesis, ii) how signal interactions of key osteotropic cytokines (TGF-β, IL-17, etc.) with/without TRAF6/adaptor-complex in the environmental milieu may affect the bone remodeling underway (by the Student-t-test & ANOVA).
Results: The results showed that: i) immature CD11c+/myeloid-DC-derived-OC-precursors/mDDOCp are significantly involved with inflammation-induced bone loss, independent of the classical Mo/MΦ-derived-OCs in the TRAF6-KO chimeras; ii) IL-17 may engage a distinctive interplay with mDDOCp before developing to CD11c+TRAF6(-/-)DDOC via TGF-β-modulated step-wise pathway to arthritic bone loss in-vivo.
Conclusions: These findings suggest that this non-discriminative signaling via TGFβ-&-IL-17 for effector-activity in CD11c+/TRAF6(-/-)mDDOCp revealed herein may underpin a new insight for the alternative osteoclastogenesis, which will require further study for its in-vivo significance; i.e., arthritic & periodontal diseases. Such proposed twist-in-turns of osteo-immune interactions involving the classical-vs.-alternative pathways for inflammation-induced bone loss will be theme-highlighted in this presentation as well.