The innate immune system consists of functionally specialized "modules" that are activated in response to a particular set of stimuli via sensors located on the surface or inside the tissue cells. These cells screen tissues for a wide range of exogenous and endogenous danger/damage-induced signals with the aim to reject or tolerate them and maintain tissue integrity. In this line of thinking, inflammation evolved as an adaptive tool for restoring tissue homeostasis. A number of diseases are mediated by a maladaptation of the innate immune response, perpetuating chronic inflammation and tissue damage. Here, we review recent evidence on the cross talk between innate immune sensors and development of rheumatoid arthritis, osteoarthritis, and aseptic loosening of total joint replacements. In relation to the latter topic, there is a growing body of evidence that aseptic loosening and periprosthetic osteolysis results from long-term maladaptation of periprosthetic tissues to the presence of by-products continuously released from an artificial joint.

• MeSH
• Lectins, C-Type metabolism   MeSH
• Humans MeSH
• Osteoarthritis immunology   physiopathology   MeSH
• Osteolysis physiopathology   MeSH
• Immunity, Innate physiology   MeSH
• Joint Prosthesis adverse effects   MeSH
• Receptor for Advanced Glycation End Products MeSH
• Receptors, Cytoplasmic and Nuclear metabolism   MeSH
• Receptors, Immunologic metabolism   MeSH
• Arthritis, Rheumatoid immunology   physiopathology   MeSH
• Nod Signaling Adaptor Proteins metabolism   MeSH
• Toll-Like Receptors metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Lectins, C-Type MeSH
• Receptor for Advanced Glycation End Products MeSH
• Receptors, Cytoplasmic and Nuclear MeSH
• Receptors, Immunologic MeSH
• Nod Signaling Adaptor Proteins MeSH
• Toll-Like Receptors MeSH

Aseptic loosening and other wear-related complications are some of the most frequent late reasons for revision of total knee arthroplasty (TKA). Periprosthetic osteolysis (PPOL) pre-dates aseptic loosening in many cases, indicating the clinical significance of this pathogenic mechanism. A variety of implant-, surgery- and host-related factors have been delineated to explain the development of PPOL. These factors influence the development of PPOL because of changes in mechanical stresses within the vicinity of the prosthetic device, excessive wear of the polyethylene liner, and joint fluid pressure and flow acting on the peri-implant bone. The process of aseptic loosening is initially governed by factors such as implant/limb alignment, device fixation quality and muscle coordination/strength. Later, large numbers of wear particles detached from TKA trigger and perpetuate particle disease, as highlighted by progressive growth of inflammatory/granulomatous tissue around the joint cavity. An increased accumulation of osteoclasts at the bone-implant interface, impairment of osteoblast function, mechanical stresses and increased production of joint fluid contribute to bone resorption and subsequent loosening of the implant. In addition, hypersensitivity and adverse reactions to metal debris may contribute to aseptic TKA failure, but should be determined more precisely. Patient activity level appears to be the most important factor when the long-term development of PPOL is considered. Surgical technique, implant design and material factors are the most important preventative factors, because they influence both the generation of wear debris and excessive mechanical stresses. New generations of bearing surfaces and designs for TKA should carefully address these important issues in extensive preclinical studies. Currently, there is little evidence that PPOL can be prevented by pharmacological intervention.

• Keywords
• Joint fluid, Knee biomechanics, Osteolysis/aseptic loosening, Total knee arthroplasty/replacement, Wear particles,
• MeSH
• Biocompatible Materials adverse effects   MeSH
• Models, Biological MeSH
• Knee Joint physiopathology   MeSH
• Humans MeSH
• Osteolysis etiology   physiopathology   MeSH
• Knee Prosthesis adverse effects   MeSH
• Prosthesis Failure MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Biocompatible Materials MeSH

Numerous studies provide detailed insight into the triggering and amplification mechanisms of the inflammatory response associated with prosthetic wear particles, promoting final dominance of bone resorption over bone formation in multiple bone multicellular units around an implant. In fact, inflammation is a highly regulated process tightly linked to simultaneous stimulation of tissue protective and regenerative mechanisms in order to prevent collateral damage of periprosthetic tissues. A variety of cytokines, chemokines, hormones and specific cell populations, including macrophages, dendritic and stem cells, attempt to balance tissue architecture and minimize inflammation. Based on this fact, we postulate that the local tissue homeostatic mechanisms more effectively regulate the pro-inflammatory/pro-osteolytic cells/pathways in patients with none/mild periprosthetic osteolysis (PPOL) than in patients with severe PPOL. In this line of thinking, 'particle disease theory' can be understood, at least partially, in terms of the failure of local tissue homeostatic mechanisms. As a result, we envision focusing current research on homeostatic mechanisms in addition to traditional efforts to elucidate details of pro-inflammatory/pro-osteolytic pathways. We believe this approach could open new avenues for research and potential therapeutic strategies.

• MeSH
• Cellular Microenvironment immunology   MeSH
• Hajdu-Cheney Syndrome etiology   immunology   prevention & control   MeSH
• Humans MeSH
• Inflammation Mediators immunology   MeSH
• Arthroplasty, Replacement, Hip * MeSH
• Osteogenesis MeSH
• Joint Prosthesis MeSH
• Prosthesis Failure etiology   MeSH
• Inflammation etiology   prevention & control   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Inflammation Mediators MeSH

BACKGROUND: Prosthetic joint infection (PJI) is an important failure mechanism of total joint arthroplasty (TJA). Here we examine whether the particular genetic variants can lead to increased susceptibility to PJI development. RESULTS: We conducted a genetic-association study to determine whether PJI could be associated with functional cytokine gene polymorphisms (CGP) influencing on innate immunity response. A case-control design was utilized and previously published criteria for PJI were included to distinguish between cases and control subjects with/without TJA. Six single nucleotide polymorphisms (SNPs) located in the genes for interleukin-1beta (SNP: IL1B-511, +3962), tumour necrosis factor alpha (TNF-308, -238) and interleukin-6 (IL6-174, nt565) were genotyped in 303 Caucasian (Czech) patients with TJA (89 with PJI / 214 without PJI), and 168 unrelated healthy Czech individuals without TJA. The results showed that carriers of the less common IL1B-511*T allele were overrepresented in the group of TJA patients with PJI (69%) in comparison with those that did not develop PJI (51%, p = 0.006, p(corr) = 0.037) and with healthy controls (55%, p = 0.04, p(corr) = N.S.). There was no significant difference in the distribution of the remaining five investigated CGPs and their haplotypes between groups. CONCLUSION: A functional variant of the gene encoding for IL-1beta was preliminarily nominated as a genetic factor contributing to the susceptibility to PJI. Our results should be independently replicated; studies on the functional relevance of IL1B gene variants in PJI are also needed.

• MeSH
• Arthroplasty * MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Association Studies MeSH
• Prosthesis-Related Infections genetics   MeSH
• Interleukin-1beta genetics   MeSH
• Interleukin-6 genetics   MeSH
• Humans MeSH
• Young Adult MeSH
• DNA Mutational Analysis MeSH
• Polymorphism, Genetic MeSH
• Joint Prosthesis adverse effects   MeSH
• Case-Control Studies MeSH
• Tumor Necrosis Factor-alpha genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Interleukin-1beta MeSH
• Interleukin-6 MeSH
• Tumor Necrosis Factor-alpha MeSH