ArticleThe Journal of biological chemistry2011
NC4 Domain of cartilage-specific collagen IX inhibits complement directly due to attenuation of membrane attack formation and indirectly through binding and enhancing activity of complement inhibitors C4B-binding protein and factor H.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- PRELP protein inhibits the formation of the complement membrane attack complex.The Journal of biological chemistry · 2012Trial
- Osteomodulin modulates the inflammatory responses via the interleukin-1 receptor 1/nuclear factor-κB signaling pathway in dental pulpitis.International journal of oral science · 2025Article
- Cadherin dysregulation in gastric cancer: insights into gene expression, pathways, and prognosis.Journal of gastrointestinal oncology · 2023Article
- The role of fibromodulin in inflammatory responses and diseases associated with inflammation.Frontiers in immunology · 2023Review
- Identification of Key Diagnostic Markers and Immune Infiltration in Osteoarthritis.Combinatorial chemistry & high throughput screening · 2023Article
- Design, Preparation, and Bioactivity Study of New Fusion Protein HB-NC4 in the Treatment of Osteoarthritis.Frontiers in bioengineering and biotechnology · 2021Article
- The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature.Frontiers in medicine · 2020Review
- [Role and progress of innate immunity in pathogenesis of osteoarthritis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2019Review
- Osteoarthritis and the Complement Cascade.Clinical medicine insights. Arthritis and musculoskeletal disorders · 2018Review
- Immune Contributions to Osteoarthritis.Current osteoporosis reports · 2017Review
- Review
- Complement factor H in host defense and immune evasion.Cellular and molecular life sciences : CMLS · 2017Review
- The complement system is activated in synovial fluid from subjects with knee injury and from patients with osteoarthritis.Arthritis research & therapy · 2016Article
- Inflammation in joint injury and post-traumatic osteoarthritis.Osteoarthritis and cartilage · 2015Review
- The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive.The Journal of rheumatology · 2015Review
- The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly.The FEBS journal · 2013Review
- The different roles of aggrecan interaction domains.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2012Review
- Review
- Osteoarthritis: a disease of the joint as an organ.Arthritis and rheumatism · 2012Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Collagen IX containing the N-terminal noncollagenous domain 4 (NC4) is unique to cartilage and a member of the family of fibril-associated collagens with both collagenous and noncollagenous domains. Collagen IX is located at the surface of fibrils formed by collagen II and a minor proportion of collagen XI, playing roles in tissue stability and integrity. The NC4 domain projects out from the fibril surface and provides sites for interaction with other matrix components such as cartilage oligomeric matrix protein, matrilins, fibromodulin, and osteoadherin. Fragmentation of collagen IX and loss of the NC4 domain are early events in cartilage degradation in joint diseases that precedes major damage of collagen II fibrils. Our results demonstrate that NC4 can function as a novel inhibitor of the complement system able to bind C4, C3, and C9 and to directly inhibit C9 polymerization and assembly of the lytic membrane attack complex. NC4 also binds the complement inhibitors C4b-binding protein and factor H and enhances their cofactor activity in degradation of activated complement components C4b and C3b. NC4 interactions with fibromodulin and osteoadherin inhibited binding to C1q and complement activation by these proteins. Taken together, our results suggest that collagen IX and its interactions with matrix components are important parts of a machinery that protects the cartilage from complement activation and chronic inflammation seen in diseases like rheumatoid arthritis.
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