Issue 4, 2021

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

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

Supplementary files

Article information

Article type
Paper
Submitted
29 Jul 2020
Accepted
21 Nov 2020
First published
10 Dec 2020

Biomater. Sci., 2021,9, 1291-1300

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements