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
• lektiny typu C metabolismus   MeSH
• lidé MeSH
• osteoartróza imunologie   patofyziologie   MeSH
• osteolýza patofyziologie   MeSH
• přirozená imunita fyziologie   MeSH
• protézy kloubů škodlivé účinky   MeSH
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory cytoplazmatické a nukleární metabolismus   MeSH
• receptory imunologické metabolismus   MeSH
• revmatoidní artritida imunologie   patofyziologie   MeSH
• signální adaptorové proteiny Nod metabolismus   MeSH
• toll-like receptory metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lektiny typu C MeSH
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory cytoplazmatické a nukleární MeSH
• receptory imunologické MeSH
• signální adaptorové proteiny Nod MeSH
• toll-like receptory 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.

• Klíčová slova
• Joint fluid, Knee biomechanics, Osteolysis/aseptic loosening, Total knee arthroplasty/replacement, Wear particles,
• MeSH
• biokompatibilní materiály škodlivé účinky   MeSH
• biologické modely MeSH
• kolenní kloub patofyziologie   MeSH
• lidé MeSH
• osteolýza etiologie   patofyziologie   MeSH
• protézy kolene škodlivé účinky   MeSH
• selhání protézy MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biokompatibilní materiály 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
• buněčné mikroprostředí imunologie   MeSH
• Hajdu-Cheney syndrom etiologie   imunologie   prevence a kontrola   MeSH
• lidé MeSH
• mediátory zánětu imunologie   MeSH
• náhrada kyčelního kloubu * MeSH
• osteogeneze MeSH
• protézy kloubů MeSH
• selhání protézy etiologie   MeSH
• zánět etiologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mediátory zánětu 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
• artroplastika * MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie MeSH
• infekce spojené s protézou genetika   MeSH
• interleukin-1beta genetika   MeSH
• interleukin-6 genetika   MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutační analýza DNA MeSH
• polymorfismus genetický MeSH
• protézy kloubů škodlivé účinky   MeSH
• studie případů a kontrol MeSH
• TNF-alfa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-1beta MeSH
• interleukin-6 MeSH
• TNF-alfa MeSH