The immunomodulatory role of irisin on osteogenesis via AMPK-mediated macrophage polarization
Abstract
Bone healing is thought to be closely related to macrophages. Irisin, a cleaved hormone-like myokine, is well known to participate in immunoregulation and regulates bone metabolism. However, whether irisin could influence osteogenesis by affecting macrophage polarization is remain unknown. Here, the present study aims to investigate the potential immunomodulatory role of irisin on macrophages polarization and its subsequent impact on osteogenesis. We demonstrated that irisin increased cell viability without toxic effect in both Raw264.7 macrophages and MC3T3-E1 cells. Furthermore, irisin treatment polarized M0 and M1 macrophages towards M2 phenotype, with increased expression of CD206-APC, ARG-1 and TGF-β1, and decreased expression of CD86-PE and TNF-α. In addition, the direct co-cultured test of Raw264.7 macrophages and pre-osteoblastic MC3T3-E1 cells showed that irisin-treated M0 and M1 macrophages promoted osteogenesis with obvious formation of mineralized particles. Interestingly, irisin exposure robustly activated AMPK-α signaling, as manifested by increased expression of phosphorylated AMPK-α. Knockdown of AMPK-α by siRNA significantly suppressed the phosphorylation of AMPK-α, abrogated irisin-induced polarization of M2 phenotype, and inhibited the osteogenic ability of Raw264.7 macrophages. Taken together, our findings showed that irisin-induced M2 polarization enhanced osteogenesis in osteoblasts, and this effect might be associated with activation of AMPK.
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Irisin favors M2 macrophage polarization and reversion of an already established M1-polarized proinflammatory state.
“It has favored not only M2 Mφ polarization, but also reversion of an already established M1-polarized proinflammatory state [59].”
In the short term, irisin might directly favor a shift from M1 to M2 phenotype, as well as decrease the expression of TLR4, TNF-α, IL-1β, MCP-1, and IL-6 by adipocytes and macrophages, while increasing IL-10 and antioxidant cellular mechanisms.
“As also shown in Figure 2 (to facilitate sequence flow, the steps appear numbered as they are introduced in the main text in italics), in the short term, irisin might directly favor a shift from M1 Mφ to a M2 phenotype [49,59], as well as decrease the expression of TLR4, TNF-α, IL-1β, MCP-1, and IL-6 by adipocytes and Mφ [51,53,59] (1a), while increasing IL-10 [59] (1b) and antioxidant cellular me”
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“Irisin Ob: ↑ [39]+; T2DM: ↓ [39]+ AE: ↑ (aerobic or resistance) [40]+ CE: ↓? (aerobic or resistance) [41]+ ↑ (via PGC-1α): cold-induced shivering [42], ↑AMP:ATP ratio (via AMPK-PGC-1α pathway), FGF21* [43], and METRNL (via ↑PGC-1α4)* [44] ↓: proinflammatory cytokines [45] (possibly via NF-kB-mediated inhibition of PGC…”
BackgroundInfluentialIrisin, an exercise-induced bioactive peptide beneficial for health promotion during aging process
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- Authors
- Ye, W., Wang, J., Lin, D., & Ding, Z.
- Affiliations
- Xiamen University (CN)
- Corresponding author
- Lin, Dasheng
- Ding, Zhenqi
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 146
- Pages
- 25-35
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W2995259075
- Cited by
- 86
- References
- 40
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 19 · 2023: 13 · 2022: 11 · 2021: 11 · 2020: 5
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Xiamen University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- irisin, bone formation, macrophage polarization, M2 macrophages, AMPK signaling, myokines, bone regeneration, osteoblasts, immunomodulation, bone metabolism, mineralization
- MeSH terms
- RAW 264.7 Cells, Animals, Fibronectins, Macrophages, Osteoblasts, Osteogenesis, Mice, AMP-Activated Protein Kinases
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