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Proinflammatory M1 Macrophages Inhibit RANKL-Induced Osteoclastogenesis
- Publication Year :
- 2016
- Publisher :
- American Society for Microbiology, 2016.
-
Abstract
- In response to a defined panel of stimuli, immature macrophages can be classified into two major phenotypes: proinflammatory (M1) and anti-inflammatory (M2). Although both phenotypes have been implicated in several chronic inflammatory diseases, their direct role in bone resorption remains unclear. The present study investigated the possible effects of M1 and M2 macrophages on RANKL-induced osteoclastogenesis. In osteoclastogenesis assays using RAW264.7 cells or bone marrow cells as osteoclast precursors, addition of M1 macrophages significantly suppressed RANKL-induced osteoclastogenesis compared to nonstimulated conditions (M0), addition of M2 macrophages, or no macrophage addition ( P < 0.05), suggesting that M1 macrophages can downregulate osteoclastogenesis. This effect was maintained when direct contact between M1 and osteoclast precursors was interrupted by cell culture insertion, indicating engagement of soluble factors released from M1. M1 macrophages developed from interferon gamma (IFN-γ) knockout (IFN-γ–KO) mice lost the ability to downregulate osteoclastogenesis. Antibody-based neutralization of interleukin-12 (IL-12), but not IL-10, produced by M1 macrophages also abrogated M1-mediated downregulation of osteoclastogenesis. Real-time PCR analyses showed that IFN-γ suppressed gene expression of NFATc1, a master regulator of osteoclastogenesis, whereas IL-12 increased the apoptosis of osteoclasts, suggesting molecular mechanisms underlying the possible roles of IFN-γ or IL-12 in M1-mediated inhibition of osteoclastogenesis. These findings were confirmed in an in vivo ligature-induced mouse periodontitis model in which adoptive transfer of M1 macrophages showed a significantly lower level of bone loss and less tartrate-resistant acid phosphatase (TRAP)-positive cell induction than M0 or M2 macrophage transfer. In conclusion, by its secretion of IFN-γ and IL-12, M1, but not M0 or M2, was demonstrated to inhibit osteoclastogenesis.
- Subjects :
- 0301 basic medicine
Immunology
Osteoclasts
Bone Marrow Cells
Enzyme-Linked Immunosorbent Assay
Biology
Microbiology
Polymerase Chain Reaction
Bone resorption
Proinflammatory cytokine
03 medical and health sciences
Interferon-gamma
Mice
Downregulation and upregulation
Osteoclast
Osteogenesis
medicine
Macrophage
Animals
Interferon gamma
Periodontitis
Mice, Knockout
Host Response and Inflammation
Analysis of Variance
Tartrate-Resistant Acid Phosphatase
Macrophages
RANK Ligand
Cell Differentiation
M2 Macrophage
Interleukin-12
Cell biology
Disease Models, Animal
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
RANKL
biology.protein
Parasitology
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c09a0d88a3692c8ab6dad4e60cbfce07