2. Academic Validation
  3. Exosomes secreted from M2-polarized macrophages inhibit osteoclast differentiation via CYLD

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

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: fuchongjian@foxmail.com.
  • 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: chentielou2010@163.com.
  • 5 Department of Stomatology, The 960th Hospital of People's Liberation Army, Jinan, China. Electronic address: Liuxin6212@outlook.com.
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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