Abstract

BackgroundAspirin has been demonstrated to promote osteoblast-mediated bone formation and inhibit osteoclast (OC)-mediated bone resorption. However, it remains unclear whether aspirin influences other immune cells during bone resorption. Dendritic cells (DCs), the most potent antigen-presenting cells, can also transdifferentiate into active OCs in the presence of receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The effects of aspirin on DC-derived OCs (DDOCs) were investigated in the current study.MethodsFlow cytometry and mixed lymphocyte reaction (MLR) assays were used for DC identification. The proliferative capacity of DCs was determined by BrdU assays. Apoptosis was examined by flow cytometry. The osteoclastic potential of DCs was tested using tartrate-resistant acid phosphatase (TRAP) staining, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). Western blotting was also used to examine signaling pathways. A mandibular bone defect model was established to assess the effect of aspirin on bone resorption.ResultsAspirin had no influence on the surface phenotype, proliferation, or apoptosis of DCs, though aspirin significantly inhibited osteoclast differentiation in RANKL-stimulated DCs. DC osteoclast differentiation was modulated by aspirin via the nuclear factor kappa B (NF-κB)/nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) signaling pathway. Aspirin treatment also had favorable therapeutic effects on bone regeneration in the bone defect model, and the number of osteoclasts was decreased.ConclusionsAspirin inhibited RANKL-induced OC differentiation in DCs via the NF-κB pathway, downregulating expression of NFATc1. Aspirin treatment promoted bone regeneration by inhibiting DDOC activation in the early stages of inflammation in a rat mandibular bone defect model.

Highlights

  • Aspirin has been demonstrated to promote osteoblast-mediated bone formation and inhibit osteoclast (OC)-mediated bone resorption

  • There is increasing evidence that immature Dendritic cells (DCs) have osteoclastogenic potential in some inflammatory pathological conditions because imDCs can transdifferentiate into active OCs after stimulation with receptor activator of nuclear factor kB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) [5, 6]

  • We examined whether aspirin regulates dendritic cell-derived osteoclast (DDOC) formation and activation

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Summary

Introduction

Aspirin has been demonstrated to promote osteoblast-mediated bone formation and inhibit osteoclast (OC)-mediated bone resorption. Dendritic cells (DCs), the most potent antigen-presenting cells, can transdifferentiate into active OCs in the presence of receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). There is increasing evidence that immature DCs (imDCs) have osteoclastogenic potential in some inflammatory pathological conditions because imDCs can transdifferentiate into active OCs after stimulation with RANKL and M-CSF [5, 6]. These findings clearly highlight a potential link between DCs and OCs

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