Autoinflammation Around AES Total Ankle Replacement Implants

Koivu, Helka; Takakubo, Yuya; Mackiewicz, Z; Al‐Samadi, Ahmed; Soininen, Antti; Peled, Nir; Kukis, Modestas; Trokovic, Nina; Konttinen, Yrjö T.

doi:10.1177/1071100715596608

Cited by 8 publications

(3 citation statements)

References 28 publications

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“…Though extensively investigated in the hip and knee arthroplasty literature, these results may not be directly extrapolated to TAA due to its differing biomechanical factors and smaller articular contact area. 93 Koivu et al 53 hypothesized that peri-implant inflammation is mediated by damage-associated molecule patterns such as HMGB1 and pattern-recognizing danger signal receptors. Histologically, ballooning osteolysis consists of mostly necrotic and acellular areas with an increased number of histiocytes containing small, sharp particles of foreign material that could represent a foreign-body reaction.…”

Section: Pathogenesismentioning

confidence: 99%

Pathogenesis, Evaluation, and Management of Osteolysis Following Total Ankle Arthroplasty

et al. 2020

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Periprosthetic osteolysis is a common occurrence after total ankle arthroplasty (TAA) and poses many challenges for the foot and ankle surgeon. Osteolysis may be asymptomatic and remain benign, or it may lead to component instability and require revision or arthrodesis. In this article, we present a current and comprehensive review of osteolysis in TAA with illustrative cases. We examine the basic science principles behind the etiology of osteolysis, discuss the workup of a patient with suspected osteolysis, and present a review of the evidence of various management strategies, including grafting of cysts, revision TAA, and arthrodesis. Level of Evidence: Level V, expert opinion.

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Section: Pathogenesismentioning

confidence: 99%

Pathogenesis, Evaluation, and Management of Osteolysis Following Total Ankle Arthroplasty

et al. 2020

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“…Accordingly, the in-vivo PLA microenvironment is characterized by enhanced fluorodeoxyglucose uptake, driving inflammation; glycolytic inhibition modulates inflammation 33 . HMGB1/ RAGE signaling is an inflammatory pathway associated with activation after exposure to polyethylene particles 34 . As part of its inflammatory role in promoting growth of pancreatic cancers, HMGB1/ RAGE signaling directly increases ATP levels by increasing mitochondrial OXPHOS 35 .…”

Section: Discussionmentioning

confidence: 99%

Elevated oxidative phosphorylation is critical for immune cell activation by polyethylene wear particles

Maduka

Kuhnert

Habeeb

et al. 2023

Journal of Immunology and Regenerative Medicine

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“…HMGB1/ RAGE signaling is an inflammatory pathway associated with activation after exposure to polyethylene particles 34 . As part of its inflammatory role in promoting growth of pancreatic cancers, HMGB1/ RAGE signaling directly increases ATP levels by increasing mitochondrial OXPHOS 35 .…”

Section: Discussionmentioning

confidence: 99%

Elevated oxidative phosphorylation is critical for immune cell activation by polyethylene wear particles

Maduka

Kuhnert

Habeeb

et al. 2022

Preprint

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Chronic inflammation is a major concern after total joint replacements (TJRs), as it is associated with bone loss, limited bone-implant integration (osseointegration), implant loosening and failure. Inflammation around implants could be directed away from adverse outcomes and toward enhanced osseointegration and improved surgical outcome. Activated macrophages exposed to polyethylene particles play a dominant inflammatory role, and exhibit elevated mitochondrial oxidative phosphorylation (OXPHOS) whose role is unclear. By probing the contribution of the electron transport chain (ETC), we show that increased oxygen consumption does not contribute to bioenergetic (ATP) levels in fibroblasts and primary bone marrow-derived macrophages activated by polyethylene particles. Rather, it generates reactive oxygen species (ROS) at complex I by increasing mitochondrial membrane potential in macrophages. Inhibition of OXPHOS in a dosedependent manner without affecting glycolysis was accomplished by targeting complex I of the ETC using either rotenone or metformin. Metformin decreased mitochondrial ROS and, subsequently, expression of proinflammatory cytokines, including IL-1β, IL-6 and MCP-1 but not TNF-a in macrophages. These results highlight the contribution of mitochondrial bioenergetics to activation of immune cells by polyethylene wear particles, offering new opportunities to modulate macrophage states toward desired clinical outcomes.

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Autoinflammation Around AES Total Ankle Replacement Implants

Abstract: Level IV, case series.

Cited by 8 publications

References 28 publications

Pathogenesis, Evaluation, and Management of Osteolysis Following Total Ankle Arthroplasty

Pathogenesis, Evaluation, and Management of Osteolysis Following Total Ankle Arthroplasty

Elevated oxidative phosphorylation is critical for immune cell activation by polyethylene wear particles

Elevated oxidative phosphorylation is critical for immune cell activation by polyethylene wear particles

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