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Issue 4, 2021
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STAT3/IL-6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle-induced aseptic prosthesis loosening

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Abstract

Background: Aseptic loosening is the main reason for surgical revision after arthroplasty. Although a series of mechanisms have been explored, a specific therapeutic target is still desired. In the present study, we explored the role of the signal transducer and activator of the transcription (STAT)/interleukin-6 (IL-6) pathway in the induction of the inflammatory response in osteoblast and osteoclast formation during aseptic prosthesis loosening. Methods: The expression of activated STAT3 was examined in osteoblasts treated with TiAl6V4 nanoparticles (TiPs) from materials used in prosthetics and specimens from particle-induced osteolysis (PIO) animal models. Inflammatory responses associated with the IL-6 family in osteoblasts were identified by Quantitative Real-time PCR. A mimicking coculture system was used to directly determine the number of activated osteoclasts in vitro, and immunohistochemical staining with tartrate-resistant acid phosphatase (TRAP) was used in vivo. CP690,550, an inhibitor of STAT3, was administered to examine the effect of STAT3 on the inflammatory response and osteoclast formation. Results: STAT3 was activated in both nanoparticle-treated osteoblasts and PIO model animals. On the one hand, the activation of STAT3 mediated nanoparticle-induced IL-6-dependent inflammatory responses in osteoblasts. On the other hand, the activation of STAT3 induced receptor activator of nuclear factor kappa B ligand (RANKL) production and stimulated osteoclast formation. The application of the STAT3 inhibitor CP690,550 reduced the production of the IL-6 family and the formation of osteoclasts both in vitro and in vivo. Conclusion: STAT3 mediated inflammation-related signalling and osteoclast activation in nanoscale wear particle-induced aseptic loosening. Inhibition of STAT3 by tofacitinib may be a potential treatment for aseptic loosening.

Graphical abstract: STAT3/IL-6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle-induced aseptic prosthesis loosening

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Supplementary files

Article information


Submitted
29 Jul 2020
Accepted
21 Nov 2020
First published
10 Dec 2020

Biomater. Sci., 2021,9, 1291-1300
Article type
Paper

STAT3/IL-6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle-induced aseptic prosthesis loosening

Z. Deng, R. Zhang, M. Li, S. Wang, G. Fu, J. Jin, Z. Wang, Y. Ma and Q. Zheng, Biomater. Sci., 2021, 9, 1291
DOI: 10.1039/D0BM01256D

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