Dataset Information

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

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-1?, and TNF? was found to be elevated. However, among these pro-inflammatory cytokines, the mRNA and protein levels of only IL-6, IL-1?, and TNF? 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-1?, and TNF? 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.

SUBMITTER: Sharma AR

PROVIDER: S-EPMC7476030 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Sharma Ashish Ranjan AR Jagga Supriya S Chakraborty Chiranjib C Lee Sang-Soo SS

Materials (Basel, Switzerland) 20200817 16

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 resu ...[more]

PMID: 32824426

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Project description:Engineered biomaterials are envisioned to replace, augment, or interact with living tissues for improving the functional deformities associated with end-stage joint pathologies. Unfortunately, wear debris from implant interfaces is the major factor leading to periprosthetic osteolysis. Fibroblast-like synoviocytes (FLSs) populate the intimal lining of the synovium and are in direct contact with wear debris. This study aimed to elucidate the effect of Ti particles as wear debris on human FLSs and the mechanism by which they might participate in the bone remodeling process during periprosthetic osteolysis. FLSs were isolated from synovial tissue from patients, and the condition medium (CM) was collected after treating FLSs with sterilized Ti particles. The effect of CM was analyzed for the induction of osteoclastogenesis or any effect on osteogenesis and signaling pathways. The results demonstrated that Ti particles could induce activation of the NFκB signaling pathway and induction of COX-2 and inflammatory cytokines in FLSs. The amount of Rankl in the conditioned medium collected from Ti particle-stimulated FLSs (Ti CM) showed the ability to stimulate osteoclast formation. The Ti CM also suppressed the osteogenic initial and terminal differentiation markers for osteoprogenitors, such as alkaline phosphate activity, matrix mineralization, collagen synthesis, and expression levels of Osterix, Runx2, collagen 1α, and bone sialoprotein. Inhibition of the WNT and BMP signaling pathways was observed in osteoprogenitors after the treatment with the Ti CM. In the presence of the Ti CM, exogenous stimulation by WNT and BMP signaling pathways failed to stimulate osteogenic activity in osteoprogenitors. Induced expression of sclerostin (SOST: an antagonist of WNT and BMP signaling) in Ti particle-treated FLSs and secretion of SOST in the Ti CM were detected. Neutralization of SOST in the Ti CM partially restored the suppressed WNT and BMP signaling activity as well as the osteogenic activity in osteoprogenitors. Our results reveal that wear debris-stimulated FLSs might affect bone loss by not only stimulating osteoclastogenesis but also suppressing the bone-forming ability of osteoprogenitors. In the clinical setting, targeting FLSs for the secretion of antagonists like SOST might be a novel therapeutic approach for preventing bone loss during inflammatory osteolysis.

Dataset Information

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

Publications

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

Similar Datasets

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