Macrophage-derived exosomes modulate wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-κB signaling

Baiqi Pan; Ziji Zhang; Xiaoyu Wu; Guoyan Xian; Xuantao Hu; Minghui Gu; Linli Zheng; Xiang Li; Lingli Long; Weishen Chen; Puyi Sheng

doi:10.1016/j.bioactmat.2023.02.028

Macrophage-derived exosomes modulate wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-κB signaling

Bioact Mater. 2023 Mar 3:26:181-193. doi: 10.1016/j.bioactmat.2023.02.028. eCollection 2023 Aug.

Authors

Baiqi Pan^{1

2}, Ziji Zhang^{1

2}, Xiaoyu Wu^{1

2}, Guoyan Xian^{1

2

3}, Xuantao Hu^{1

2}, Minghui Gu^{1

2}, Linli Zheng^{1

2}, Xiang Li^{2

4}, Lingli Long⁵, Weishen Chen^{1

2}, Puyi Sheng^{1

2}

Affiliations

¹ Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.
² Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China.
³ Université de Paris, CNRS, INSERM, B3OA, Paris, France.
⁴ Department of Spine Surgery, The first affiliated hospital of Sun Yat-sen University, China.
⁵ Research Center of Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, China.

Abstract

Aseptic prosthesis loosening (APL) is one of the most prevalent complications associated with arthroplasty. The main cause is the periprosthetic osteolysis induced by wear particles. However, the specific mechanisms of crosstalk between immune cells and osteoclasts/osteoblasts during osteolysis are unclear. In this study, we report the role and mechanism of macrophage-derived exosomes in wear particle-induced osteolysis. The results of exosomes up-taken experiments revealed that osteoblast and mature osteoclasts capture macrophage-derived exosomes (M-Exo). Next-generation sequencing and RT-qPCR on M-Exo revealed that exosomal microRNA miR-3470b was downregulated in wear particle-induced osteolysis. The results of analysis on Luciferase reporter assays/fluorescence in situ hybridization (FISH)/immunofluorescence (IF)/immunohistochemistry (IHC) and co-culture experiments demonstrated that wear particles induced osteoclast differentiation by increasing the expression of NFatc1 via M-Exo miR-3470b targeting TAB3/ NF-κB signaling. We also illustrate that engineered exosomes enriching miR-3470b facilitated to suppressed the osteolysis; the microenvironment enriching with miR-3470b could suppress wear particle-induced osteolysis via inhibition of TAB3/ NF-κB in vivo. In summary, our findings indicate that macrophage-derived exosomes transfer to osteoclasts to induce osteolysis in wear particle-induced APL. Engineering exosomes enriching with miR-3470b might be a novel strategy for the targeting treatment of bone resorption-related diseases.

Keywords: Aseptic prothesis loosening; Exosome; Inflammatory osteolysis; Macrophage; Non-coding RNA.