Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles

Yang-Lin Wu; Chen-Hui Zhang; Yun Teng; Ying Pan; Nai-Cheng Liu; Pei-Xin Liu; Xu Zhu; Xin-Lin Su; Jun Lin

doi:10.1186/s40779-022-00404-0

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Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles

RESEARCH | Updated：2023-05-10

- Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles
- Military Medical Research Vol. 10, Issue 2, Pages: 191-206(2023)
- Affiliations：
  
  1.Department of Orthopaedics, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Centre of Soochow University, Suzhou 215001, Jiangsu, China
  2.Department of Orthopaedics, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, Jiangsu, China
  3.Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
- Author bio：
  
  * linjun@suda.edu.cn
- Funds：
- DOI：10.1186/s40779-022-00404-0
  CLC：
- Published：2023-04
- Accepted：
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Cite this article as: Wu YL, Zhang CH, Teng Y, Pan Y, Liu NC, Liu PX, et al. Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles. Mil Med Res. 2022;9(1):46.
DOI：

Cite this article as: Wu YL, Zhang CH, Teng Y, Pan Y, Liu NC, Liu PX, et al. Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles. Mil Med Res. 2022;9(1):46. DOI： 10.1186/s40779-022-00404-0.

摘要

Abstract

Background:

Wear particles-induced osteolysis is a major long-term complication after total joint arthroplasty. Up to now

there is no effective treatment for wear particles-induced osteolysis except for the revision surgery

which is a heavy psychological and economic burden to patients. A metabolite of gut microbiota

short chain fatty acids (SCFAs)

has been reported to be beneficial for many chronic inflammatory diseases. This study aimed to investigate the therapeutic effect of SCFAs on osteolysis.

Methods:

A model of inflammatory osteolysis was established by applying CoCrMo alloy particles to mouse calvarium. After two weeks of intervention

the anti-inflammatory effects of SCFAs on wear particle-induced osteolysis were evaluated by micro-CT analysis and immunohistochemistry staining.

In vitro

study

lipopolysaccharide (LPS) primed bone marrow-derived macrophages (BMDMs) and Tohoku hospital pediatrics-1 (THP-1) macrophages were stimulated with CoCrMo particles to activate inflammasome in the presence of acetate (C2)

propionate (C3)

and butyrate (C4). Western blotting

enzyme-linked immunosorbent assay

and immunofluorescence were used to detect the activation of NLRP3 inflammasome. The effects of SCFAs on osteoclasts were evaluate by qRT-PCR

Western blotting

immunofluorescence

and tartrate-resistant acid phosphatase (TRAP) staining. Additionally

histone deacetylase (HDAC) inhibitors

agonists of GPR41

GPR43

and GPR109A were applied to confirm the underlying mechanism of SCFAs on the inflammasome activation of macrophages and osteoclastogenesis.

Results:

C3 and C4 but not C2 could alleviate wear particles-induced osteolysis with fewer bone erosion pits (

0.001)

higher level of bone volume to tissue volume (BV/TV

0.001)

bone mineral density (BMD

0.001)

and a lower total porosity (

0.001). C3 and C4 prevented CoCrMo alloy particles-induced ASC speck formation and nucleation-induced oligomerization

suppressing the cleavage of caspase-1 (

0.05) and IL-1β (

0.05) stimulated by CoCrMo alloy particles. C3 and C4 also inhibited the generation of gasdermin D-N-terminal fragment (GSDMD-NT) to regulate pyroptosis. Besides

C3 and C4 have a negative impact on osteoclast differentiation (

0.05) and its function (

0.05)

affecting the podosome arrangement and morphologically normal podosome belts formation.

Conclusions:

Our work showed that C3 and C4 are qualified candidates for the treatment of wear particle-induced osteolysis.

关键词

Keywords

references

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