Fibroblast-Like-Synoviocytes Mediate Secretion of Pro-Inflammatory Cytokines via ERK and JNK MAPKs in Ti-Particle-Induced Osteolysis.

Ashish Ranjan Sharma,Supriya Jagga,Chiranjib Chakraborty,Sang-Soo Lee

doi:10.3390/ma13163628

Ashish Ranjan Sharma, Supriya Jagga + Show 2 more

Open Access

https://doi.org/10.3390/ma13163628

Copy DOI

Journal: Materials	Publication Date: Aug 17, 2020
Citations: 11	License type: CC BY 4.0

Affiliation: Chuncheon Sacred Heart Hospital, Hallym University

Abstract

Biomaterials are designed to replace and augment living tissues in order to provide functional support to skeletal deformities. However, wear debris produced from the interfaces of metal implants initiates inflammatory bone loss, causing periprosthetic osteolysis. Lately, fibroblast-like synoviocytes (FLS) have been shown to play a role in wear-debris-induced osteolysis. Thus, here we have tried to understand the underlying mechanism of FLS involvement in wear-debris-induced osteolysis. Our results demonstrate that the effects of Ti particle (1:100 cell-to-Ti particle ratio) on FLS can induce Cox-2 expression and activate NFkB signaling. Moreover, the mRNA expression of pro-inflammatory cytokines such as IL-6, IL-8, IL-11, IL-1β, and TNFα was found to be elevated. However, among these pro-inflammatory cytokines, the mRNA and protein levels of only IL-6, IL-1β, and TNFα were found to be significantly higher. Ti particles activated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) as an early response in FLS. Co-inhibition of ERK and JNK signaling pathways by their specific inhibitors (PD9805 and SP600125, respectively) resulted in the suppression of mRNA and protein levels of IL-6, IL-1β, and TNFα in FLS. Taken together, targeting ERK and JNK MAPKs in FLS might provide a therapeutic option for reducing the secretion of bone-resorbing pro-inflammatory cytokines, thus preventing periprosthetic osteolysis.

Highlights

Degenerative skeletal diseases such as osteoarthritis, rheumatoid arthritis, and osteoporosis lead to skeletal disabilities and often require total joint arthroplasty (TJA) to provide restoration of function and pain relief
Several cell-to-Ti particles ratios were used for the treatment of SW982 for 24 h, and any effects of Ti particles on the cell viability and cell toxicity were analyzed by MTT and Lactate Dehydrogenase Activity (LDH) assays, respectively
The study provides evidence of the fact that the Ti particles can stimulate fibroblast-like synoviocytes (FLS) to secrete a significant amount of pro-inflammatory cytokines such as IL-6, IL-1β, and TNFα in the synovium

Summary

Introduction

Degenerative skeletal diseases such as osteoarthritis, rheumatoid arthritis, and osteoporosis lead to skeletal disabilities and often require total joint arthroplasty (TJA) to provide restoration of function and pain relief. Millions of people (>1.3 million) undergo TJA [3]. Within 10 years of surgery, up to 20% of these cases require a revision [4]. As young and more active populations are undergoing TJA with insufficient implant durability, more TJAs revisions are expected [5]. Particulate debris can be produced by diverse kinds of processes, including corrosion, micromotion, and oxidative reactions of implants [7]. The buildup of particulate debris from the interface of orthopedic implants can trigger biological response leading to aseptic loosening and immense bone loss, requiring revision of surgery for the patients [8].

Objectives

Methods

Results

Conclusion