{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:15:09Z","timestamp":1791461709454,"version":"4.3.4"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Components derived from cartilage have been suggested to maintain the inflammation in joints in arthritis. Small leucine-rich repeat proteins (SLRPs) are structural components of cartilage important in organizing the meshwork of extracellular matrix components. It has recently been shown that the SLRP fibromodulin interacts with complement initiator C1q, leading to complement activation. The complement response is limited since fibromodulin also interacts with the complement inhibitor factor H. We have now found that osteoadherin, chondroadherin, fibromodulin, and proline arginine-rich end leucine-rich repeat protein bind to the complement inhibitor C4b-binding protein (C4BP). Using direct binding assays with C4BP fragments and C4BP mutants lacking individual domains in combination with electron microscopy, we have demonstrated that mainly the central core of C4BP mediated binding to SLRPs. Binding of SLRPs to C4BP did not affect its ability to inhibit complement. Osteoadherin, fibromodulin, and chondroadherin, which bind C1q and activate complement, were found to cause significantly higher C9 deposition in C4BP-depleted serum compared with Igs, indicating that the level of complement activation initiated by SLRPs is regulated by simultaneous binding to C4BP. A similar dual binding of C1q and complement inhibitors was observed previously for other endogenous ligands (amyloid, prions, C-reactive protein, and apoptotic cells) but not for exogenous activators (bacteria-bound Igs). These interactions can be significant during inflammatory joint diseases, such as rheumatoid arthritis, where cartilage is degraded, and cartilage components are released into synovial fluid, where they can interact with factors of the complement system.<\/jats:p>","DOI":"10.4049\/jimmunol.182.3.1518","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:01:40Z","timestamp":1397847700000},"page":"1518-1525","source":"Crossref","is-referenced-by-count":50,"title":["Complement Inhibitor C4b-Binding Protein Interacts Directly with Small Glycoproteins of the Extracellular Matrix"],"prefix":"10.1093","volume":"182","author":[{"given":"Kaisa E","family":"Happonen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Wallenberg Laboratory, University Hospital Malm\u00f6, Lund University , Malm\u00f6,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas P","family":"Sj\u00f6berg","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Wallenberg Laboratory, University Hospital Malm\u00f6, Lund University , Malm\u00f6,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"M\u00f6rgelin","sequence":"additional","affiliation":[{"name":"Department of Infection Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick","family":"Heineg\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Biomedical Center, Lund University , Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Wallenberg Laboratory, University Hospital Malm\u00f6, Lund University , Malm\u00f6,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,2,1]]},"reference":[{"key":"2026012806222475900_R1","first-page":"6596","article-title":"Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator.","volume-title":"Proc. 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Cell Biol.","year":"1998"},{"key":"2026012806222475900_R17","first-page":"2601","article-title":"A collagen-binding 59-kd protein (fibromodulin) is structurally related to the small interstitial proteoglycans PG-S1 and PG-S2 (decorin).","volume-title":"EMBO J.","year":"1989"},{"key":"2026012806222475900_R18","first-page":"1","article-title":"Leucine-rich repeat glycoproteins of the extracellular matrix.","volume-title":"Matrix Biol.","year":"1998"},{"key":"2026012806222475900_R19","first-page":"25639","article-title":"The primary structure of a basic leucine-rich repeat protein, PRELP, found in connective tissues.","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026012806222475900_R20","first-page":"26","article-title":"Identification of tyrosine sulfation in extracellular leucine-rich repeat proteins using mass spectrometry.","volume-title":"J. Biol. 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Rheumatol.","year":"1987"},{"key":"2026012806222475900_R35","first-page":"1143","article-title":"Evaluation of classical complement pathway activation in rheumatoid arthritis: measurement of C1q-C4 complexes as novel activation products.","volume-title":"Arthritis Rheum.","year":"2006"},{"key":"2026012806222475900_R36","first-page":"1531","article-title":"Synovial fluid levels of complement SC5b-9 and fragment Bb are elevated in patients with rheumatoid arthritis.","volume-title":"Arthritis Rheum.","year":"1991"},{"key":"2026012806222475900_R37","first-page":"1208","article-title":"Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis.","volume-title":"Eur. J. Immunol.","year":"2004"},{"key":"2026012806222475900_R38","first-page":"4340","article-title":"A role for complement in antibody-mediated inflammation: C5-deficient DBA\/1 mice are resistant to collagen-induced arthritis.","volume-title":"J. 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