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

2021 ◽  
Author(s):  
Zhantao Deng ◽  
Ruiying Zhang ◽  
Mengyuan Li ◽  
Shuai Wang ◽  
Guangtao Fu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Wear Particle ◽  
Osteoclast Formation ◽  
Wear Particles ◽  
Rankl Expression ◽  
Prosthesis Loosening ◽  
Aseptic Prosthesis Loosening ◽  
Nanoscale Wear

Our study demonstrated wear particles, which are generated by the abrasion of implanted prostheses, could induced STAT3 activation in osteoblasts. And further, inflammatory responses and RANKL expression would activate osteoclasts and cause osteolysis.

scholarly journals Particle Disease: A Current Review of the Biological Mechanisms in Periprosthetic Osteolysis After Hip Arthroplasty

2016 ◽  
Vol 10 (1) ◽  
pp. 241-251 ◽  
Author(s):  
Erhan Sukur ◽  
Yunus Emre Akman ◽  
Yusuf Ozturkmen ◽  
Fatih Kucukdurmaz
Keyword(s):  
Aseptic Loosening ◽  
Hip Arthroplasty ◽  
Inflammatory Responses ◽  
Therapeutic Interventions ◽  
Wear Particles ◽  
Biological Mechanisms ◽  
Prosthesis Loosening ◽  
Periprosthetic Osteolysis ◽  
Aseptic Prosthesis Loosening

Background:Inflammatory responses to wear debris cause osteolysis that leads to aseptic prosthesis loosening and hip arthroplasty failure. Although osteolysis is usually associated with aseptic loosening, it is rarely seen around stable implants. Aseptic implant loosening is a simple radiologic phenomenon, but a complex immunological process. Particulate debris produced by implants most commonly causes osteolysis, and this is called particle-associated periprosthetic osteolysis (PPO).Objective:The objective of this review is to outline the features of particle-associated periprosthetic osteolysis to allow the physician to recognise this condition and commence early treatment, thereby optimizing patient outcome.Methods:A thorough literature search was performed using available databases, including Pubmed, to cover important research published covering particle-associated PPO.Results:Although osteolysis causes bone resorption, clinical, animal, andin vitrostudies of particle bioreactivity suggest that particle-associated PPO represents the culmination of several biological reactions of many cell types, rather than being caused solely by the osteoclasts. The biological activity is highly dependent on the characteristics and quantity of the wear particles.Conclusion:Despite advances in total hip arthroplasty (THA), particle-associated PPO and aseptic loosening continue to be major factors that affect prosthetic joint longevity. Biomarkers could be exploited as easy and objective diagnostic and prognostic targets that would enable testing for osteolysis after THA. Further research is needed to identify new biomarkers in PPO. A comprehensive understanding of the underlying biological mechanisms is crucial for developing new therapeutic interventions to reverse or suppress biological responses to wear particles.

SIRT1 protects osteoblasts against particle-induced inflammatory responses and apoptosis in aseptic prosthesis loosening

2017 ◽  
Vol 49 ◽  
pp. 541-554 ◽  
Author(s):  
Zhantao Deng ◽  
Zhenheng Wang ◽  
Jiewen Jin ◽  
Yong Wang ◽  
Nirong Bao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Prosthesis Loosening ◽  
Aseptic Prosthesis Loosening

scholarly journals The Recombinant Protein EphB4-Fc Changes the Ti Particle-Mediated Imbalance of OPG/RANKL via EphrinB2/EphB4 Signaling Pathway and Inhibits the Release of Proinflammatory Factors In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yu-Wei Ge ◽  
Kai Feng ◽  
Xiao-Liang Liu ◽  
Hong-Fang Chen ◽  
Zhen-Yu Sun ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Osteoclast Differentiation ◽  
Wear Particle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Wear Particles ◽  
Proinflammatory Factors

Aseptic loosening caused by wear particles is one of the common complications after total hip arthroplasty. We investigated the effect of the recombinant protein ephB4-Fc (erythropoietin-producing human hepatocellular receptor 4) on wear particle-mediated inflammatory response. In vitro, ephrinB2 expression was analyzed using siRNA-NFATc1 (nuclear factor of activated T-cells 1) and siRNA-c-Fos. Additionally, we used Tartrate-resistant acid phosphatase (TRAP) staining, bone pit resorption, Enzyme-linked immunosorbent assay (ELISA), as well as ephrinB2 overexpression and knockdown experiments to verify the effect of ephB4-Fc on osteoclast differentiation and function. In vivo, a mouse skull model was constructed to test whether the ephB4-Fc inhibits osteolysis and inhibits inflammation by micro-CT, H&E staining, immunohistochemistry, and immunofluorescence. The gene expression of ephrinB2 was regulated by c-Fos/NFATc1. Titanium wear particles activated this signaling pathway to the promoted expression of the ephrinB2 gene. However, ephrinB2 protein can be activated by osteoblast membrane receptor ephB4 to inhibit osteoclast differentiation. In in vivo experiments, we found that ephB4 could regulate Ti particle-mediated imbalance of OPG/RANKL, and the most important finding was that ephB4 relieved the release of proinflammatory factors. The ephB4-Fc inhibits wear particle-mediated osteolysis and inflammatory response through the ephrinB2/EphB4 bidirectional signaling pathway, and ephrinB2 ligand is expected to become a new clinical drug therapeutic target.

scholarly journals The Role of TLR and Chemokine in Wear Particle-Induced Aseptic Loosening

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Qiaoli Gu ◽  
Qin Shi ◽  
Huilin Yang
Keyword(s):  
Inflammatory Response ◽  
Aseptic Loosening ◽  
Osteoclast Differentiation ◽  
Adaptor Protein ◽  
Wear Particle ◽  
Cellular Migration ◽  
Cellular Interaction ◽  
Wear Particles ◽  
Orthopaedic Implants ◽  
Inhibitory Protein

Wear particle-induced periprosthetic osteolysis remains the principal cause of aseptic loosening of orthopaedic implants. Monocytes/macrophages phagocytose wear particles and release cytokines that induce inflammatory response. This response promotes osteoclast differentiation and osteolysis. The precise mechanisms by which wear particles are recognized and induce the accumulation of inflammatory cells in the periprosthetic tissue have not been fully elucidated. Recent studies have shown that toll-like receptors (TLRs) contribute to the cellular interaction with wear particles. Wear particles are recognized by monocytes/macrophages through TLRs coupled with the adaptor protein MyD88. After the initial interaction, wear particles induce both local and systemic migration of monocytes/macrophages to the periprosthetic region. The cellular migration is mediated through chemokines including interleukin-8, macrophage chemotactic protein-1, and macrophage inhibitory protein-1 in the periprosthetic tissues. Interfering with chemokine-receptor axis can inhibit cellular migration and inflammatory response. This paper highlights recent advances in TLR, and chemokine participated in the pathogenesis of aseptic loosening. A comprehensive understanding of the recognition and migration mechanism is critical to the development of measures that prevent wear particle-induced aseptic loosening of orthopaedic implants.

scholarly journals Deficiency of Lipin2 Results in Enhanced NF-κB Signaling and Osteoclast Formation in RAW-D Murine Macrophages

2021 ◽  
Vol 22 (6) ◽  
pp. 2893
Author(s):  
Asami Watahiki ◽  
Seira Hoshikawa ◽  
Mitsuki Chiba ◽  
Hiroshi Egusa ◽  
Satoshi Fukumoto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Osteoclast Formation ◽  
Fine Tuning ◽  
Nuclear Accumulation ◽  
Innate Immune Responses ◽  
Osteoclastic Resorption ◽  
Bone Disorder ◽  
Proinflammatory Responses ◽  
Potential Therapeutic Intervention

Lipin2 is a phosphatidate phosphatase that plays critical roles in fat homeostasis. Alterations in Lpin2, which encodes lipin2, cause the autoinflammatory bone disorder Majeed syndrome. Lipin2 limits lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. However, little is known about the precise molecular mechanisms underlying its anti-inflammatory function. In this study, we attempted to elucidate the molecular link between the loss of lipin2 function and autoinflammatory bone disorder. Using a Lpin2 knockout murine macrophage cell line, we showed that lipin2 deficiency enhances innate immune responses to LPS stimulation through excessive activation of the NF-κB signaling pathway, partly because of TAK1 signaling upregulation. Lipin2 depletion also enhanced RANKL-mediated osteoclastogenesis and osteoclastic resorption activity accompanied by NFATc1 dephosphorylation and increased nuclear accumulation. These results suggest that lipin2 suppresses the development of autoinflammatory bone disorder by fine-tuning proinflammatory responses and osteoclastogenesis in macrophages. Therefore, this study provides insights into the molecular pathogenesis of monogenic autoinflammatory bone disorders and presents a potential therapeutic intervention.

scholarly journals Peptide VSAK maintains tissue glucose uptake and attenuates pro-inflammatory responses caused by LPS in an experimental model of the systemic inflammatory response syndrome: a PET study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ismael Luna-Reyes ◽  
Eréndira G. Pérez-Hernández ◽  
Blanca Delgado-Coello ◽  
Miguel Ángel Ávila-Rodríguez ◽  
Jaime Mas-Oliva
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Glucose Uptake ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
Systemic Inflammatory Response ◽  
Positron Emission ◽  
Inflammatory Molecules ◽  
Circulating Levels ◽  
Lps Treatment

AbstractThe present investigation using Positron Emission Tomography shows how peptide VSAK can reduce the detrimental effects produced by lipopolysaccharides in Dutch dwarf rabbits, used to develop the Systemic Inflammatory Response Syndrome (SIRS). Animals concomitantly treated with lipopolysaccharides (LPS) and peptide VSAK show important protection in the loss of radiolabeled-glucose uptake observed in diverse organs when animals are exclusively treated with LPS. Treatment with peptide VSAK prevented the onset of changes in serum levels of glucose and insulin associated with the establishment of SIRS and the insulin resistance-like syndrome. Treatment with peptide VSAK also allowed an important attenuation in the circulating levels of pro-inflammatory molecules in LPS-treated animals. As a whole, our data suggest that peptide VSAK might be considered as a candidate in the development of new therapeutic possibilities focused on mitigating the harmful effects produced by lipopolysaccharides during the course of SIRS.

Abstract 1769: Caveolin-1 Regulates TGF-Beta Signaling in Cardiac Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Shelley Miyasato ◽  
Oana Bollt ◽  
Joyce Pike ◽  
Ann Hashimoto ◽  
Ralph V Shohet ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Ventricular Function ◽  
Cardiac Remodeling ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Fibrous Tissue ◽  
Left Ventricular ◽  
Caveolin 1 ◽  
Post Surgery ◽  
Smad2 Phosphorylation

In cardiac fibrosis, fibrous tissue replaces healthy contractile tissue. The regulation of these processes is controlled in large part by transforming growth factor-β (TGF-β). Caveolin-1 (cav1) regulates TGF-β signaling by either sequestering the TGF-β receptor complex or enhancing its degradation. Thus, cav1 may prevent TGF-β directed fibrosis. To investigate the role of cav1 in cardiac remodeling, we performed left ventricular cryoinjury in Cav1-deficient (Cav1−/−) mice and wild-type controls. Ventricular function was followed by echocardiography, and 3, 14, and 30 days after surgery, cardiac RNA and protein were analyzed for inflammatory responses, connective tissue and TGF-β signaling related proteins. Cryoinjured WT presented reduced cav1 expression. Concurrently, evidence of activation of TGF-β signaling was measured as shown by increase of Smad2 phosphorylation. Moreover Cav1−/− cryoinjured hearts had enhanced Smad2 phosphorylation. Collagen gene expression was transiently upregulated in cryoinjured WT mice 3 days post surgery (2.5-fold) and this elevation persisted in Cav1−/− hearts (3.5-fold at 14 days). The level of collagenases (mmp-8 and -13) expression was dramatically increased in the 3-day cryoinjured WT but not in Cav1−/− mice. As a result, augmented collagen deposition, resulting from increased collagen expression and reduced degradation by collagenases, was observed by Masson’s trichrome and picrosirius staining in injured Cav1−/− hearts. WT mice had a transient decline in fractional shortening (FS) but function returned to baseline by 30 days post-injury. In contrast, cryoinjured Cav1−/− mice had a significant lower % FS after 30 days compared to baseline or to cryoinjured WT (67.4 ± 9.6, 76 ± 11, 76.9 ± 5.5, respectively). Moreover Cav1−/− mice presented an altered inflammatory response following cryoinjury. Reduced macrophage infiltrates and IL-6 level of expression were also measured in cryoinjured Cav1−/− mice. These data indicate that in absence of caveolae, TGF-β signaling is enhanced, and this leads to a disordered inflammatory response and suboptimal cardiac remodeling that may impair left ventricular function.

Brake Wear Particle Size and Shape Analysis of Non-Asbestos Organic (NAO) and Semi Metallic Brake Pad

2014 ◽  
Vol 71 (2) ◽  
Author(s):  
Hussain, S. ◽  
M.K Abdul Hamid ◽  
A.R Mat Lazim ◽  
A.R. Abu Bakar
Keyword(s):  
Particle Size ◽  
Wear Particle ◽  
Brake Disc ◽  
Wear Particles ◽  
Brake Pad ◽  
Brake Pads ◽  
Size And Shape ◽  
Brake Wear Particles ◽  
Brake Wear ◽  
Particle Size And Shape

Brake wear particles resulting from friction between the brake pad and disc are common in brake system. In this work brake wear particles were analyzed based on the size and shape to investigate the effects of speed and load applied to the generation of brake wear particles. Scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX) was used to identify the size, shape and element compositions of these particles. Two types of brake pads were studied which are non-asbestos organic and semi metallic brake pads. Results showed that the size and shape of the particles generatedvary significantly depending on the applied brake load, and less significantly on brake disc speed. The wear particle becomes bigger with increasing applied brake pressure. The wear particle size varies from 300 nm to 600 µm, and contained elements such as carbon, oxygen, magnesium, aluminum, sulfur and iron.

scholarly journals Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

2014 ◽  
Vol 11 (93) ◽  
pp. 20130962 ◽  
Author(s):  
S. B. Goodman ◽  
E. Gibon ◽  
J. Pajarinen ◽  
T.-H. Lin ◽  
M. Keeney ◽  
...  
Keyword(s):  
Pathologic Fracture ◽  
Wear Particle ◽  
Wear Particles ◽  
Implant Loosening ◽  
Orthopaedic Implants ◽  
Periprosthetic Osteolysis ◽  
Joint Replacements ◽  
Local Inhibition ◽  
Tissue Healing ◽  
Chronic Inflammatory Reaction

Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants.

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