Exosomes secreted from M2-polarized macrophages inhibit osteoclast differentiation via CYLD

  • Tissue Cell. 2024 Nov 30:93:102645. doi: 10.1016/j.tice.2024.102645.
Zi-Yan Guo  1 ,  Nan-Nan Yin  2 ,  Xiao-Fei Li  2 ,  Meng-Meng Wang  2 ,  Xiao-Na Sui  2 ,  Cai-di Jiang  1 ,  Ming-Hua Xu  1 ,  Xiao-E Jia  1 ,  Chong-Jian Fu  3 ,  Tie-Lou Chen  4 ,  Xin Liu  5
Affiliations
  • 1. Department of Stomatology, Changhai Hospital Affiliated to Naval Medical University, 168 Changhai Road, Shanghai 200433, China.
  • 2. Department of Stomatology, The 960th Hospital of People's Liberation Army, Jinan, China.
  • 3. Department of Stomatology, The 960th Hospital of People's Liberation Army, Jinan, China. Electronic address: [email protected].
  • 4. Department of Periodontal, Military Dental Center, Changhai Hospital Affiliated to Naval Medical University, 168 Changhai Road, Yang Pu District, Shanghai, 200433, China. Electronic address: [email protected].
  • 5. Department of Stomatology, The 960th Hospital of People's Liberation Army, Jinan, China. Electronic address: [email protected].
PMID: 39671756 DOI: 10.1016/j.tice.2024.102645
Abstract

Objective: Bone resorption mediated by osteoclast differentiation induces the occurrence of bone-related diseases. Macrophages, an origin of osteoclasts, whose M2 type can reduce inflammation-induced bone damage. We aimed to investigate the effect of M2 macrophage-derived exosomes on osteoclast formation and elucidate its underlying mechanism.

Materials and methods: Exosomes were isolated from M2 macrophages (M2-exo) and were used to treat osteoclast-like cells. Osteoclast formation was evaluated using tartrate-resistant Acid Phosphatase, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. The molecular mechanism of M2-exo function was analyzed by qRT-PCR, phosphor-kinase array analysis, and Western blotting.

Results: M2-exo was internalized by osteoclasts and inhibited osteoclast differentiation in vitro. Moreover, CYLD was highly expressed in M2 macrophages and M2-exo-treated osteoclasts, and knockdown of it abrogated the inhibition of osteoclast differentiation caused by M2-exo. Additionally, CYLD suppressed the phosphorylation of STAT3, and STAT3 Activator colivelin reversed the inhibition of osteoclast differentiation induced by CYLD overexpression.

Conclusion: M2-exo inhibits osteoclast differentiation via delivering CYLD, which inactivates STAT3 signaling. These findings may provide a novel therapeutic option for bone diseases including periodontitis.

Keywords
CYLD; Exosome; M2 macrophages; Osteoclast differentiation; STAT3.
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