{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:19:43Z","timestamp":1793657983520,"version":"4.5.1"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The complement system is locally activated after joint injuries and leads to the deposition of the terminal complement complex (TCC). Sublytic TCC deposition is associated with phenotypical alterations of human articular chondrocytes (hAC) and enhanced release of inflammatory cytokines. Chronic inflammation is a known driver of chondrosenescence in osteoarthritis (OA). Therefore, we investigated whether TCC deposition contributes to stress-induced premature senescence (SIPS) during aging <jats:italic>in vivo<\/jats:italic> and after <jats:italic>ex vivo<\/jats:italic> cartilage injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Femoral condyles of male 13-week-old and 72-week-old CD59-ko (higher TCC deposition), C6-deficient (insufficient TCC formation), and C57BL\/6 (WT) mice were collected to assess age-related OA. Furthermore, macroscopically intact human and porcine cartilage explants were traumatized and cultured with\/without 30% human serum (HS) to activate the complement system. Explants were additionally treated with clusterin (CLU, TCC inhibitor), N-acetylcysteine (NAC, antioxidant), Sarilumab (IL-6 receptor inhibitor), STAT3-IN-1 (STAT3 inhibitor), or IL-1 receptor antagonist (IL-1RA) in order to investigate the consequences of TCC deposition. Gene and protein expression of senescence-associated markers such as CDKN1A and CDKN2A was determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the murine aging model, CD59-ko mice developed after 72 weeks more severe OA compared to C6-deficient and WT mice. mRNA analysis revealed that the expression of Cdkn1a, Cdkn2a, Tp53, Il1b, and Il6 was significantly increased in the cartilage of CD59-ko mice. In human cartilage, trauma and subsequent stimulation with HS increased mRNA levels of CDKN1A, CDKN2A, and IL6, while inhibition of TCC formation by CLU reduced the expression. Antioxidative therapy with NAC had no anti-senescent effect. In porcine tissue, HS exposure and trauma had additive effects on the number of CDKN2A-positive cells, while Sarilumab, STAT-IN-1, and IL-1RA reduced CDKN2A expression by trend.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that complement activation and consequent TCC deposition is associated with chondrosenescence in age-related and trauma-induced OA. We provided evidence that the SIPS-like phenotype is more likely induced by TCC-mediated cytokine release rather than oxidative stress. Overall, targeting TCC formation could be a future approach to attenuate OA progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1470907","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:13:37Z","timestamp":1736835217000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Terminal complement complex deposition on chondrocytes promotes premature senescence in age- and trauma-related osteoarthritis"],"prefix":"10.3389","volume":"15","author":[{"given":"Leonie","family":"Ruths","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Hengge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciosa Q.","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Haffner-Luntzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Ignatius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Riegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: a disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051560","article-title":"Pathomechanisms of posttraumatic osteoarthritis: chondrocyte behavior and fate in a precarious environment","volume":"21","author":"Riegger","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2010.03.001","article-title":"Epidemiology of osteoarthritis","volume":"26","author":"Zhang","year":"2010","journal-title":"Clin Geriatr Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4085\/1062-6050-51.5.08","article-title":"Epidemiology of posttraumatic osteoarthritis","volume":"52","author":"Thomas","year":"2017","journal-title":"J Athl Train"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2023.2185133","article-title":"Emerging therapeutic targets for osteoarthritis","volume":"27","author":"Hadzic","year":"2023","journal-title":"Expert Opin Ther Targets"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-00979-5","article-title":"Failure of cartilage regeneration: emerging hypotheses and related therapeutic strategies","volume":"19","author":"Muthu","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.01.004","article-title":"Anaphylatoxins and their corresponding receptors as potential drivers in cartilage calcification during osteoarthritis progression","volume":"32","author":"Ruths","year":"2024","journal-title":"Osteoarthritis Cartilage"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/biom13020216","article-title":"Functional loss of terminal complement complex protects rabbits from injury-induced osteoarthritis on structural and cellular level","volume":"13","author":"Riegger","year":"2023","journal-title":"Biomolecules"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1177\/0363546515602248","article-title":"Differential interactive effects of cartilage traumatization and blood exposure in vitro and in vivo","volume":"43","author":"Joos","year":"2015","journal-title":"Am J Sports Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1177\/1179544117751430","article-title":"Osteoarthritis and the complement cascade","volume":"11","author":"Silawal","year":"2018","journal-title":"Clin Med Insights Arthritis Musculoskelet Disord"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2022.170815","article-title":"Involvement of complement peptides C3a and C5a in osteoarthritis pathology","volume":"154","author":"Schafer","year":"2022","journal-title":"Peptides"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2543","article-title":"Identification of a central role for complement in osteoarthritis","volume":"17","author":"Wang","year":"2011","journal-title":"Nat Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-1123-x","article-title":"The complement system is activated in synovial fluid from subjects with knee injury and from patients with osteoarthritis","volume":"18","author":"Struglics","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-021-00872-x","article-title":"Complement as driver of systemic inflammation and organ failure in trauma, burn, and sepsis","volume":"43","author":"Mannes","year":"2021","journal-title":"Semin Immunopathol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.05.006","article-title":"The role of complement in trauma and fracture healing","volume":"25","author":"Huber-Lang","year":"2013","journal-title":"Semin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2020.02.006","article-title":"Complement membrane attack complex: new roles, mechanisms of action, and therapeutic targets","volume":"190","author":"Xie","year":"2020","journal-title":"Am J Pathol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.918551","article-title":"Complement membrane attack complex is an immunometabolic regulator of NLRP3 activation and IL-18 secretion in human macrophages","volume":"13","author":"Jimenez-Duran","year":"2022","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.01.004","article-title":"Crucial role of the terminal complement complex in chondrocyte death and hypertrophy after cartilage trauma","volume":"28","author":"Riegger","year":"2020","journal-title":"Osteoarthritis Cartilage"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36441-z","article-title":"Structural basis for membrane attack complex inhibition by CD59","volume":"14","author":"Couves","year":"2023","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1497-2","article-title":"Anaphylatoxin receptors and complement regulatory proteins in human articular and non-articular chondrocytes: interrelation with cytokines","volume":"350","author":"Schulze-Tanzil","year":"2012","journal-title":"Cell Tissue Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3823","article-title":"Cellular senescence: from physiology to pathology","volume":"15","author":"Munoz-Espin","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"S96","DOI":"10.1097\/01.blo.0000143818.74887.b1","article-title":"Chondrocyte senescence, joint loading and osteoarthritis","volume":"427","author":"Martin","year":"2004","journal-title":"Clin Orthop Relat Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4324","article-title":"Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment","volume":"23","author":"Jeon","year":"2017","journal-title":"Nat Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glw154","article-title":"Transplanted senescent cells induce an osteoarthritis-like condition in mice","volume":"72","author":"Xu","year":"2017","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071106","article-title":"In vitro characterization of doxorubicin-mediated stress-induced premature senescence in human chondrocytes","volume":"11","author":"Kirsch","year":"2022","journal-title":"Cells"},{"key":"B26","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.joca.2015.07.008","article-title":"Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regeneration","volume":"24","author":"Ashraf","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2784","article-title":"A complex secretory program orchestrated by the inflammasome controls paracrine senescence","volume":"15","author":"Acosta","year":"2013","journal-title":"Nat Cell Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: the dark side of tumor suppression","volume":"5","author":"Coppe","year":"2010","journal-title":"Annu Rev Pathol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-023-00489-y","article-title":"Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review","volume":"28","author":"Riegger","year":"2023","journal-title":"Cell Mol Biol Lett"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.728100","article-title":"Aging, cell senescence, the pathogenesis and targeted therapies of osteoarthritis","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Pharmacol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2004.08.001","article-title":"Molecular basis for complement component 6 (C6) deficiency in rats and mice","volume":"209","author":"Bhole","year":"2004","journal-title":"Immunobiology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102310","article-title":"Role of C3a receptors, C5a receptors, and complement protein C6 deficiency in collagen antibody-induced arthritis in mice","volume":"188","author":"Banda","year":"2012","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v99.10.3707","article-title":"Crry, but not CD59 and DAF, is indispensable for murine erythrocyte protection in vivo from spontaneous complement attack","volume":"99","author":"Miwa","year":"2002","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.02.007","article-title":"Comparison of joint degeneration and pain in male and female mice in DMM model of osteoarthritis","volume":"29","author":"Hwang","year":"2021","journal-title":"Osteoarthritis Cartilage"},{"key":"B35","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.joca.2006.11.005","article-title":"Osteoarthritis severity is sex dependent in a surgical mouse model","volume":"15","author":"Ma","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/art.42530","article-title":"Age-associated changes in knee osteoarthritis, pain-related behaviors, and dorsal root ganglia immunophenotyping of male and female mice","volume":"75","author":"Geraghty","year":"2023","journal-title":"Arthritis Rheumatol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.molimm.2016.06.004","article-title":"Sex matters: Systemic complement activity of female C57BL\/6J and BALB\/cJ mice is limited by serum terminal pathway components","volume":"76","author":"Kotimaa","year":"2016","journal-title":"Mol Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23010","article-title":"OARSI osteoarthritis cartilage histopathology assessment system: A biomechanical evaluation in the human knee","volume":"34","author":"Waldstein","year":"2016","journal-title":"J Orthop Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91453","article-title":"Increase of cell surface vimentin is associated with vimentin network disruption and subsequent stress-induced premature senescence in human chondrocytes","volume":"12","author":"Riegger","year":"2023","journal-title":"Elife"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.07.019","article-title":"Antioxidative therapy in an ex vivo human cartilage trauma-model: attenuation of trauma-induced cell loss and ECM-destructive enzymes by N-acetyl cysteine","volume":"24","author":"Riegger","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"key":"B41","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/jcmm.13295","article-title":"Striking a new path in reducing cartilage breakdown: combination of antioxidative therapy and chondroanabolic stimulation after blunt cartilage trauma","volume":"22","author":"Riegger","year":"2018","journal-title":"J Cell Mol Med"},{"key":"B42","first-page":"v","article-title":"Osteoporosis and osteoarthritis","volume":"1226","author":"van Wijnen","year":"2015","journal-title":"Methods Mol Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/art.37782","article-title":"Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2","volume":"65","author":"Gavriilidis","year":"2013","journal-title":"Arthritis Rheumatism"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-015-4498-0","article-title":"A porcine knee model is valid for use in the evaluation of arthroscopic skills: A pilot study","volume":"474","author":"Martin","year":"2016","journal-title":"Clin Orthop Relat Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.138.1.246","article-title":"Recovery of human neutrophils from complement attack: removal of the membrane attack complex by endocytosis and exocytosis","volume":"138","author":"Morgan","year":"1987","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-005-0004-1","article-title":"Emission of membrane vesicles: roles in complement resistance, immunity and cancer","volume":"27","author":"Pilzer","year":"2005","journal-title":"Springer Semin Immunopathol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1042\/bj2310205","article-title":"The recovery of human polymorphonuclear leucocytes from sublytic complement attack is mediated by changes in intracellular free calcium","volume":"231","author":"Morgan","year":"1985","journal-title":"Biochem J"},{"key":"B48","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/0143-4160(86)90042-4","article-title":"Intracellular Ca2+ and cell injury: a paradoxical role of Ca2+ in complement membrane attack","volume":"7","author":"Morgan","year":"1986","journal-title":"Cell Calcium"},{"key":"B49","article-title":"Sublytic concentrations of the membrane attack complex of complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear factor-kappa B activation","volume":"150","author":"Kilgore","year":"1997","journal-title":"Am J Pathol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002972","article-title":"Alloantibody and complement promote T cell-mediated cardiac allograft vasculopathy through noncanonical nuclear factor-kappaB signaling in endothelial cells","volume":"128","author":"Jane-Wit","year":"2013","journal-title":"Circulation"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00727-x","article-title":"The senescence-associated secretory phenotype and its physiological and pathological implications","volume":"25","author":"Wang","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1023177","article-title":"The role of IL-6\/JAK2\/STAT3 signaling pathway in cancers","volume":"12","author":"Huang","year":"2022","journal-title":"Front Oncol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abn7082","article-title":"Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner","volume":"15","author":"Liao","year":"2022","journal-title":"Sci Signal"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq2395","article-title":"Inhibition of a signaling modality within the gp130 receptor enhances tissue regeneration and mitigates osteoarthritis","volume":"15","author":"Shkhyan","year":"2023","journal-title":"Sci Transl Med"},{"key":"B55","doi-asserted-by":"publisher","first-page":"R262","DOI":"10.1186\/ar4107","article-title":"Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model","volume":"14","author":"Tsuchida","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/science.adj7050","article-title":"Cellular senescence in normal physiology","volume":"384","author":"de Magalhaes","year":"2024","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.10.588843","article-title":"p53-induced GDF-15 expression promotes a pro-regenerative response in human chondrocytes upon cartilage injury","author":"Marques","year":"2024","journal-title":"bioRxiv.2024.04.10.588843"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204881","article-title":"Development of a DNA damage-induced senescence model in osteoarthritic chondrocytes","volume":"15","author":"Georget","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2022.03.076","article-title":"Complement C3-alpha and C3-beta levels in synovial fluid but not in blood correlate with the severity of osteoarthritis research society international histopathological grades in primary knee osteoarthritis","volume":"37","author":"Cheng","year":"2022","journal-title":"J Arthroplasty"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158689","article-title":"The complement system, aging, and aging-related diseases","volume":"23","author":"Zheng","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02664","article-title":"Age and sex-associated changes of complement activity and complement levels in a healthy caucasian population","volume":"9","author":"Gaya da Costa","year":"2018","journal-title":"Front Immunol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1177\/1759720X12467868","article-title":"Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations","volume":"5","author":"Sokolove","year":"2013","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"B63","doi-asserted-by":"publisher","first-page":"12","DOI":"10.15386\/mpr-1422","article-title":"The evaluation of oxidative stress in osteoarthritis","volume":"93","author":"Zahan","year":"2020","journal-title":"Med Pharm Rep"},{"key":"B64","doi-asserted-by":"publisher","first-page":"R134","DOI":"10.1186\/ar4591","article-title":"Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis","volume":"16","author":"Furman","year":"2014","journal-title":"Arthritis Res Ther"},{"key":"B65","article-title":"Synthesis of classical pathway complement components by chondrocytes","volume":"88","author":"Bradley","year":"1996","journal-title":"Immunology"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06051-6","article-title":"Inhibition of complement C3 prevents osteoarthritis progression in Guinea pigs by blocking STAT1 activation","volume":"7","author":"Xu","year":"2024","journal-title":"Commun Biol"},{"key":"B67","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2106\/00004623-198062050-00001","article-title":"Arthroscopy in acute traumatic hemarthrosis of the knee. Incidence of anterior cruciate tears and other injuries","volume":"62","author":"Noyes","year":"1980","journal-title":"J Bone Joint Surg Am"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.11.008","article-title":"Blood in the joint: effects of hemarthrosis on meniscus health and repair techniques","volume":"29","author":"Lyons","year":"2021","journal-title":"Osteoarthritis Cartilage"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.08.008","article-title":"Inflammation, the complement system and the diseases of aging","author":"McGeer","year":"2005","journal-title":"Neurobiol Aging"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2004.01.005","article-title":"Inflammation and neurodegeneration in Parkinson\u2019s disease","author":"McGeer","year":"2004","journal-title":"Parkinsonism Relat Disord"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9394(02)01624-0","article-title":"A role for local inflammation in the formation of drusen in the aging eye","volume":"134","author":"Anderson","year":"2002","journal-title":"Am J Ophthalmol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00539","article-title":"C-reactive protein as a mediator of complement activation and inflammatory signaling in age-related macular degeneration","volume":"9","author":"Chirco","year":"2018","journal-title":"Front Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S298307","article-title":"Complement profiles in patients with amyotrophic lateral sclerosis: A prospective observational cohort study","volume":"14","author":"Kjaeldgaard","year":"2021","journal-title":"J Inflammation Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-023-01738-z","article-title":"Soluble terminal complement complex blood levels are elevated in schizophrenia","volume":"274","author":"Savukoski","year":"2024","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/cells12060887","article-title":"Terminal complement activation is induced by factors released from endplate tissue of disc degeneration patients and stimulates expression of catabolic enzymes in annulus fibrosus cells","volume":"12","author":"Kuhn","year":"2023","journal-title":"Cells"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-020-06592-4","article-title":"Terminal complement complex formation is associated with intervertebral disc degeneration","volume":"30","author":"Teixeira","year":"2021","journal-title":"Eur Spine J"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-021-06901-5","article-title":"Interleukin-1beta and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue","volume":"30","author":"Teixeira","year":"2021","journal-title":"Eur Spine J"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1002\/path.4669","article-title":"Molecular response of chorioretinal endothelial cells to complement injury: implications for macular degeneration","volume":"238","author":"Zeng","year":"2016","journal-title":"J Pathol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1470907\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:13:47Z","timestamp":1736835227000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1470907\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,14]]},"references-count":78,"alternative-id":["10.3389\/fimmu.2024.1470907"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1470907","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,14]]},"article-number":"1470907"}}