{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T19:29:22Z","timestamp":1786562962191,"version":"build-2736575974"},"reference-count":115,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,30]]},"abstract":"<jats:p>Serpins (serine proteinase inhibitors) are an ancient superfamily of structurally similar proteins, the majority of which use an elegant suicide inhibition mechanism to target serine proteinases. Despite likely evolving from a single common ancestor, the 36 human serpins have established roles regulating diverse biological processes, such as blood coagulation, embryonic development and extracellular matrix (ECM) turnover. Genetic mutations in serpin genes underpin a host of monogenic disorders \u2014 collectively termed the \u2018serpinopathies\u2019 \u2014 but serpin dysregulation has also been shown to drive pathological mechanisms in many common diseases. Osteoarthritis is a degenerative joint disorder, characterised by the progressive destruction of articular cartilage. This breakdown of the cartilage is driven by the metalloproteinases, and it has long been established that an imbalance of metalloproteinases to their inhibitors is of critical importance. More recently, a role for serine proteinases in cartilage destruction is emerging; including the activation of latent matrix metalloproteinases and cell-surface receptors, or direct proteolysis of the ECM. Serpins likely regulate these processes, as well as having roles beyond serine proteinase inhibition. Indeed, serpins are routinely observed to be highly modulated in osteoarthritic tissues and fluids by \u2018omic analysis, but despite this, they are largely ignored. Confusing nomenclature and an underappreciation for the role of serine proteinases in osteoarthritis (OA) being the likely causes. In this narrative review, serpin structure, biochemistry and nomenclature are introduced, and for the first time, their putative importance in maintaining joint tissues \u2014 as well as their dysregulation in OA \u2014 are explored.<\/jats:p>","DOI":"10.1042\/bst20201231","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T17:43:43Z","timestamp":1618249423000},"page":"1013-1026","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Serpins in cartilage and osteoarthritis: what do we know?"],"prefix":"10.1042","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6262-3575","authenticated-orcid":false,"given":"David J.","family":"Wilkinson","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal Biology and Ageing Sciences, Institute of Life Course and Medical Sciences, University of Liverpool, William Henry Duncan Building, 6 W Derby St, Liverpool L7 8TX, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"2021111916100832500_BST-2020-1231C1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1479-7364-7-22","article-title":"Update of the human and mouse SERPIN gene superfamily","volume":"7","year":"2013","journal-title":"Hum. Genom."},{"key":"2021111916100832500_BST-2020-1231C2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/0268-960X(88)90013-6","article-title":"Antithrombin III deficiency","volume":"2","year":"1988","journal-title":"Blood Rev."},{"key":"2021111916100832500_BST-2020-1231C3","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/0006-291X(80)90867-0","article-title":"A surprising new protein superfamily containing ovalbumin, antithrombin-III, and alpha 1-proteinase inhibitor","volume":"95","year":"1980","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111916100832500_BST-2020-1231C4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/0968-0004(85)90011-8","article-title":"\u03b11-Antitrypsin and the serpins: variation and countervariation","volume":"10","year":"1985","journal-title":"Trends Biochem. Sci."},{"key":"2021111916100832500_BST-2020-1231C5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fmed.2019.00025","article-title":"SERPINs-from trap to treatment","volume":"6","year":"2019","journal-title":"Front. Med. (Lausanne)"},{"key":"2021111916100832500_BST-2020-1231C6","doi-asserted-by":"publisher","first-page":"37810","DOI":"10.1074\/jbc.M305088200","article-title":"Conserved Ser residues, the shutter region, and speciation in serpin evolution","volume":"278","year":"2003","journal-title":"J. Biol. Chem."},{"issue":"Pt 2","key":"2021111916100832500_BST-2020-1231C7","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3184\/003685001783239032","article-title":"The serpins: nature's molecular mousetraps","volume":"84","year":"2001","journal-title":"Sci. Prog."},{"key":"2021111916100832500_BST-2020-1231C8","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/j.1538-7836.2011.04360.x","article-title":"Serpin structure, function and dysfunction","volume":"9","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"2021111916100832500_BST-2020-1231C9","doi-asserted-by":"publisher","first-page":"4808","DOI":"10.1073\/pnas.96.9.4808","article-title":"Formation of the covalent serpin-proteinase complex involves translocation of the proteinase by more than 70 A and full insertion of the reactive center loop into beta-sheet A","volume":"96","year":"1999","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916100832500_BST-2020-1231C10","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/35038119","article-title":"Structure of a serpin-protease complex shows inhibition by deformation","volume":"407","year":"2000","journal-title":"Nature"},{"key":"2021111916100832500_BST-2020-1231C11","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1042\/BCJ20160014","article-title":"Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance","volume":"473","year":"2016","journal-title":"Biochem. J."},{"key":"2021111916100832500_BST-2020-1231C12","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1110\/ps.9.7.1274","article-title":"Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease","volume":"9","year":"2000","journal-title":"Protein Sci."},{"key":"2021111916100832500_BST-2020-1231C13","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00739-7","article-title":"Targeting dysregulation of metalloproteinase activity in osteoarthritis","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"2021111916100832500_BST-2020-1231C14","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/bph.14173","article-title":"Serine proteinases in the turnover of the cartilage extracellular matrix in the joint: implications for therapeutics","volume":"176","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"2021111916100832500_BST-2020-1231C15","doi-asserted-by":"publisher","first-page":"3644","DOI":"10.1002\/art.24046","article-title":"Emerging roles of serine proteinases in tissue turnover in arthritis","volume":"58","year":"2008","journal-title":"Arthritis Rheum."},{"key":"2021111916100832500_BST-2020-1231C16","doi-asserted-by":"publisher","first-page":"10266","DOI":"10.1074\/jbc.RA119.006974","article-title":"Collagenolytic matrix metalloproteinases antagonize proteinase-activated receptor-2 activation, providing insights into extracellular matrix turnover","volume":"294","year":"2019","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C17","doi-asserted-by":"publisher","first-page":"16693","DOI":"10.1038\/s41598-017-17028-3","article-title":"The serine proteinase hepsin is an activator of pro-matrix metalloproteinases: molecular mechanisms and implications for extracellular matrix turnover","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"2021111916100832500_BST-2020-1231C18","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1002\/art.40133","article-title":"Matriptase induction of metalloproteinase-dependent aggrecanolysis in vitro and in vivo: promotion of osteoarthritic cartilage damage by multiple mechanisms","volume":"69","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"2021111916100832500_BST-2020-1231C19","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1124\/pr.110.002733","article-title":"Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases","volume":"62","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"2021111916100832500_BST-2020-1231C20","doi-asserted-by":"publisher","first-page":"118","DOI":"10.4103\/0975-7406.76489","article-title":"Acute-phase proteins: as diagnostic tool","volume":"3","year":"2011","journal-title":"J. Pharm. Bioallied Sci."},{"key":"2021111916100832500_BST-2020-1231C21","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.joca.2018.12.015","article-title":"Identification of long non-coding RNAs expressed in knee and hip osteoarthritic cartilage","volume":"27","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111916100832500_BST-2020-1231C22","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.joca.2007.05.008","article-title":"Subtractive gene expression profiling of articular cartilage and mesenchymal stem cells: serpins as cartilage-relevant differentiation markers","volume":"16","year":"2008","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111916100832500_BST-2020-1231C23","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1177\/1947603518809403","article-title":"SERPINA9 and SERPINB2: novel cartilage lineage differentiation markers of human mesenchymal stem cells with kartogenin","volume":"12","year":"2021","journal-title":"Cartilage"},{"key":"2021111916100832500_BST-2020-1231C24","doi-asserted-by":"publisher","first-page":"15007","DOI":"10.1073\/pnas.1309648110","article-title":"Anti-inflammatory and immunomodulatory properties of alpha1-antitrypsin without inhibition of elastase","volume":"110","year":"2013","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916100832500_BST-2020-1231C25","doi-asserted-by":"publisher","first-page":"606083","DOI":"10.1155\/2013\/606083","article-title":"Alpha 1-antichymotrypsin, an inflammatory protein overexpressed in the brains of patients with Alzheimer's disease, induces tau hyperphosphorylation through c-Jun N-terminal kinase activation","volume":"2013","year":"2013","journal-title":"Int. J. Alzheimers Dis."},{"key":"2021111916100832500_BST-2020-1231C26","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1136\/ard.34.3.225","article-title":"Proteinase inhibitors in rheumatoid arthritis","volume":"34","year":"1975","journal-title":"Ann. Rheum. Dis."},{"key":"2021111916100832500_BST-2020-1231C27","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1002\/1529-0131(199909)42:9&lt;1936::AID-ANR20&gt;3.0.CO;2-K","article-title":"Induction of alpha1-antitrypsin synthesis in human articular chondrocytes by interleukin-6-type cytokines: evidence for a local acute-phase response in the joint","volume":"42","year":"1999","journal-title":"Arthritis Rheum."},{"key":"2021111916100832500_BST-2020-1231C28","doi-asserted-by":"publisher","first-page":"R180","DOI":"10.1186\/ar4369","article-title":"Proteomic profiling and functional characterization of early and late shoulder osteoarthritis","volume":"15","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"2021111916100832500_BST-2020-1231C29","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1479-5876-9-21","article-title":"Alpha-1 antitrypsin protein and gene therapies decrease autoimmunity and delay arthritis development in mouse model","volume":"9","year":"2011","journal-title":"J. Transl. Med."},{"key":"2021111916100832500_BST-2020-1231C30","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1002\/1529-0131(200109)44:9&lt;2084::AID-ART359&gt;3.0.CO;2-R","article-title":"Activation of procollagenases is a key control point in cartilage collagen degradation: interaction of serine and metalloproteinase pathways","volume":"44","year":"2001","journal-title":"Arthritis Rheum."},{"key":"2021111916100832500_BST-2020-1231C31","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.matbio.2014.08.013","article-title":"Quantitative proteomics at different depths in human articular cartilage reveals unique patterns of protein distribution","volume":"40","year":"2014","journal-title":"Matrix Biol."},{"key":"2021111916100832500_BST-2020-1231C32","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1172\/JCI0213462","article-title":"Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis","volume":"109","year":"2002","journal-title":"J. Clin. Invest."},{"key":"2021111916100832500_BST-2020-1231C33","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s13075-019-1923-x","article-title":"Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation","volume":"21","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"2021111916100832500_BST-2020-1231C34","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12974-017-0944-0","article-title":"Prophylactic inhibition of neutrophil elastase prevents the development of chronic neuropathic pain in osteoarthritic mice","volume":"14","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"2021111916100832500_BST-2020-1231C35","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.3892\/etm.2017.4684","article-title":"Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-kappaB in a rat model","volume":"14","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"2021111916100832500_BST-2020-1231C36","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s00018-003-3240-3","article-title":"Human clade B serpins (ov-serpins) belong to a cohort of evolutionarily dispersed intracellular proteinase inhibitor clades that protect cells from promiscuous proteolysis","volume":"61","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"2021111916100832500_BST-2020-1231C37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1399-0039.2008.01059.x","article-title":"The role of serpins in vertebrate immunity","volume":"72","year":"2008","journal-title":"Tissue Antigens"},{"key":"2021111916100832500_BST-2020-1231C38","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1002\/art.34392","article-title":"Fibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis","volume":"64","year":"2012","journal-title":"Arthritis Rheum."},{"key":"2021111916100832500_BST-2020-1231C39","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1159\/000214823","article-title":"Molar antithrombin concentration in normal human plasma","volume":"13","year":"1983","journal-title":"Haemostasis"},{"key":"2021111916100832500_BST-2020-1231C40","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1172\/JCI117358","article-title":"Studies of thrombin-induced proteoglycan release in the degradation of human and bovine cartilage","volume":"94","year":"1994","journal-title":"J. Clin. Invest."},{"key":"2021111916100832500_BST-2020-1231C41","doi-asserted-by":"publisher","first-page":"14683","DOI":"10.1073\/pnas.94.26.14683","article-title":"The anticoagulant activation of antithrombin by heparin","volume":"94","year":"1997","journal-title":"Proc. Natl Acad. Sci. U.SA."},{"key":"2021111916100832500_BST-2020-1231C42","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1161\/01.ATV.0000256471.22437.88","article-title":"Heparin cofactor II modulates the response to vascular injury","volume":"27","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021111916100832500_BST-2020-1231C43","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1172\/JCI0213432","article-title":"Heparin cofactor II inhibits arterial thrombosis after endothelial injury","volume":"109","year":"2002","journal-title":"J. Clin. Invest."},{"key":"2021111916100832500_BST-2020-1231C44","doi-asserted-by":"publisher","first-page":"3920","DOI":"10.1016\/S0021-9258(18)53560-2","article-title":"Interaction of heparin cofactor II with biglycan and decorin","volume":"268","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C45","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1002\/art.37823","article-title":"Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues","volume":"65","year":"2013","journal-title":"Arthritis Rheum."},{"key":"2021111916100832500_BST-2020-1231C46","doi-asserted-by":"publisher","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"Uniprot: a worldwide hub of protein knowledge","volume":"47","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2021111916100832500_BST-2020-1231C47","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3389\/fonc.2018.00024","article-title":"Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications","volume":"8","year":"2018","journal-title":"Front. Oncol."},{"key":"2021111916100832500_BST-2020-1231C48","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1182\/blood-2012-03-415869","article-title":"Crystal structures of protease nexin-1 in complex with heparin and thrombin suggest a 2-step recognition mechanism","volume":"120","year":"2012","journal-title":"Blood"},{"key":"2021111916100832500_BST-2020-1231C49","doi-asserted-by":"publisher","first-page":"2756","DOI":"10.1172\/JCI116893","article-title":"Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis","volume":"92","year":"1993","journal-title":"J. Clin. Invest."},{"key":"2021111916100832500_BST-2020-1231C50","doi-asserted-by":"publisher","first-page":"3677","DOI":"10.1523\/JNEUROSCI.0277-07.2007","article-title":"Mice lacking protease nexin-1 show delayed structural and functional recovery after sciatic nerve crush","volume":"27","year":"2007","journal-title":"J. Neurosci."},{"key":"2021111916100832500_BST-2020-1231C51","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1073\/pnas.051630698","article-title":"Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1","volume":"98","year":"2001","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916100832500_BST-2020-1231C52","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s000110050742","article-title":"Effects of tetracyclines on the production of matrix metalloproteinases and plasminogen activators as well as of their natural inhibitors, tissue inhibitor of metalloproteinases-1 and plasminogen activator inhibitor-1","volume":"50","year":"2001","journal-title":"Inflamm. Res."},{"key":"2021111916100832500_BST-2020-1231C53","doi-asserted-by":"publisher","first-page":"e0135979","DOI":"10.1371\/journal.pone.0135979","article-title":"SERPINE2 inhibits IL-1alpha-Induced MMP-13 expression in human chondrocytes: involvement of ERK\/NF-kappaB\/AP-1 pathways","volume":"10","year":"2015","journal-title":"PLoS One"},{"key":"2021111916100832500_BST-2020-1231C54","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1016\/j.joca.2009.05.005","article-title":"Role of hypoxia-inducible factor-1 alpha in the regulation of plasminogen activator activity in rat knee joint chondrocytes","volume":"17","year":"2009","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111916100832500_BST-2020-1231C55","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.3892\/mmr.2013.1654","article-title":"Regulation of plasminogen activator activity and expression by cyclic mechanical stress in rat mandibular condylar chondrocytes","volume":"8","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"2021111916100832500_BST-2020-1231C56","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1002\/art.24680","article-title":"Regulation of plasminogen activator inhibitor 1 expression in human osteoarthritic chondrocytes by fluid shear stress: role of protein kinase Calpha","volume":"60","year":"2009","journal-title":"Arthritis Rheum."},{"key":"2021111916100832500_BST-2020-1231C57","first-page":"1863","article-title":"Plasmin, plasminogen activators and inhibitor in human osteoarthritic cartilage","volume":"18","year":"1991","journal-title":"J. Rheumatol."},{"key":"2021111916100832500_BST-2020-1231C58","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/978-3-0348-7442-7_20","article-title":"Recombinant human protease nexin-1 prevents articular cartilage-degradation in the rabbit","volume":"39","year":"1993","journal-title":"Agents Actions Suppl."},{"key":"2021111916100832500_BST-2020-1231C59","doi-asserted-by":"publisher","first-page":"30563","DOI":"10.1038\/srep30563","article-title":"The involvement of protease nexin-1 (PN1) in the pathogenesis of intervertebral disc (IVD) degeneration","volume":"6","year":"2016","journal-title":"Sci. Rep."},{"key":"2021111916100832500_BST-2020-1231C60","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1080\/14397595.2018.1525018","article-title":"Plasminogen activator inhibitor-1 is involved in interleukin-1beta-induced matrix metalloproteinase expression in murine chondrocytes","volume":"29","year":"2019","journal-title":"Mod. Rheumatol."},{"key":"2021111916100832500_BST-2020-1231C61","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1186\/s12891-017-1752-5","article-title":"Plasminogen activator inhibitor-1 deficiency enhances subchondral osteopenia after induction of osteoarthritis in mice","volume":"18","year":"2017","journal-title":"BMC Musculoskelet. Disord."},{"key":"2021111916100832500_BST-2020-1231C62","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1136\/annrheumdis-2018-214786","article-title":"CircSERPINE2 protects against osteoarthritis by targeting miR-1271 and ETS-related gene","volume":"78","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"2021111916100832500_BST-2020-1231C63","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/nrc3484","article-title":"The effects of PEDF on cancer biology: mechanisms of action and therapeutic potential","volume":"13","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"2021111916100832500_BST-2020-1231C64","doi-asserted-by":"publisher","first-page":"33310","DOI":"10.1074\/jbc.M801287200","article-title":"Pigment epithelium-derived factor binds to hyaluronan. Mapping of a hyaluronan binding site","volume":"283","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C65","doi-asserted-by":"publisher","first-page":"45400","DOI":"10.1074\/jbc.M208339200","article-title":"Mapping the type I collagen-binding site on pigment epithelium-derived factor. Implications for its antiangiogenic activity","volume":"277","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C66","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1021\/bi0206558","article-title":"Dual-site recognition of different extracellular matrix components by anti-angiogenic\/neurotrophic serpin, PEDF","volume":"42","year":"2003","journal-title":"Biochemistry"},{"key":"2021111916100832500_BST-2020-1231C67","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12891-017-1410-y","article-title":"Pigment epithelium-derived factor (PEDF) mediates cartilage matrix loss in an age-dependent manner under inflammatory conditions","volume":"18","year":"2017","journal-title":"BMC Musculoskelet Disord."},{"key":"2021111916100832500_BST-2020-1231C68","doi-asserted-by":"publisher","first-page":"7183516","DOI":"10.1155\/2017\/7183516","article-title":"PEDF is associated with the termination of chondrocyte phenotype and catabolism of cartilage tissue","volume":"2017","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"2021111916100832500_BST-2020-1231C69","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1160\/TH13-01-0080","article-title":"Haemarthrosis stimulates the synovial fibrinolytic system in haemophilic mice","volume":"110","year":"2013","journal-title":"Thromb. Haemost."},{"key":"2021111916100832500_BST-2020-1231C70","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/jth.12467","article-title":"Antiplasmin, but not amiloride, prevents synovitis and cartilage damage following hemarthrosis in hemophilic mice","volume":"12","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"2021111916100832500_BST-2020-1231C71","doi-asserted-by":"publisher","first-page":"13243","DOI":"10.1073\/pnas.1208072109","article-title":"Molecular basis for the action of the collagen-specific chaperone Hsp47\/SERPINH1 and its structure-specific client recognition","volume":"109","year":"2012","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916100832500_BST-2020-1231C72","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1074\/jbc.TM118.002812","article-title":"Roles of the endoplasmic reticulum-resident, collagen-specific molecular chaperone Hsp47 in vertebrate cells and human disease","volume":"294","year":"2019","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C73","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.ajhg.2010.01.034","article-title":"Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta","volume":"86","year":"2010","journal-title":"Am. J. Hum. Genet."},{"issue":"Pt 5","key":"2021111916100832500_BST-2020-1231C74","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1242\/jcs.089748","article-title":"The molecular chaperone Hsp47 is essential for cartilage and endochondral bone formation","volume":"125","year":"2012","journal-title":"J. Cell Sci."},{"key":"2021111916100832500_BST-2020-1231C75","doi-asserted-by":"publisher","first-page":"10394","DOI":"10.1038\/s41598-017-10740-0","article-title":"Ancestry & molecular evolutionary analyses of heat shock protein 47\u2005kDa (HSP47\/SERPINH1)","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"2021111916100832500_BST-2020-1231C76","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00418-004-0697-6","article-title":"Expression of collagen type I and type II in consecutive stages of human osteoarthritis","volume":"122","year":"2004","journal-title":"Histochem. Cell Biol."},{"key":"2021111916100832500_BST-2020-1231C77","doi-asserted-by":"publisher","first-page":"4905","DOI":"10.1038\/s41598-019-41355-2","article-title":"Glycosaminoglycans influence enzyme activity of MMP2 and MMP2\/TIMP3 complex formation - insights at cellular and molecular level","volume":"9","year":"2019","journal-title":"Sci. Rep."},{"key":"2021111916100832500_BST-2020-1231C78","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.chembiol.2014.07.014","article-title":"Sulfated glycosaminoglycans control the extracellular trafficking and the activity of the metalloprotease inhibitor TIMP-3","volume":"21","year":"2014","journal-title":"Chem. Biol."},{"key":"2021111916100832500_BST-2020-1231C79","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/B978-0-12-385950-1.00007-9","article-title":"Serpin-glycosaminoglycan interactions","volume":"501","year":"2011","journal-title":"Methods Enzymol."},{"key":"2021111916100832500_BST-2020-1231C80","doi-asserted-by":"publisher","first-page":"11079","DOI":"10.1073\/pnas.162232399","article-title":"Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism","volume":"99","year":"2002","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916100832500_BST-2020-1231C81","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/0049-3848(90)90257-D","article-title":"The effect of sulfation on the anticoagulant and antithrombin III-binding properties of a heparin fraction with low affinity for antithrombin III","volume":"57","year":"1990","journal-title":"Thromb. Res."},{"key":"2021111916100832500_BST-2020-1231C82","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1186\/s13075-020-02352-3","article-title":"Heparan sulfate functions are altered in the osteoarthritic cartilage","volume":"22","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"2021111916100832500_BST-2020-1231C83","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.ajpath.2018.11.011","article-title":"Heparan sulfate proteoglycan synthesis is dysregulated in human osteoarthritic cartilage","volume":"189","year":"2019","journal-title":"Am. J. Pathol."},{"key":"2021111916100832500_BST-2020-1231C84","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1074\/jbc.M112.393322","article-title":"Differential regulation of extracellular tissue inhibitor of metalloproteinases-3 levels by cell membrane-bound and shed low density lipoprotein receptor-related protein 1","volume":"288","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C85","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.matbio.2016.03.007","article-title":"MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1","volume":"56","year":"2016","journal-title":"Matrix Biol."},{"key":"2021111916100832500_BST-2020-1231C86","doi-asserted-by":"publisher","first-page":"6462","DOI":"10.1074\/jbc.M113.545376","article-title":"Low density lipoprotein receptor-related protein 1 (LRP1)-mediated endocytic clearance of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4): functional differences of non-catalytic domains of ADAMTS-4 and ADAMTS-5 in LRP1 binding","volume":"289","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C87","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1096\/fj.12-216671","article-title":"LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage","volume":"27","year":"2013","journal-title":"FASEB J."},{"key":"2021111916100832500_BST-2020-1231C88","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/B978-0-12-386471-0.00002-X","article-title":"Serpin-enzyme receptors LDL receptor-related protein 1","volume":"499","year":"2011","journal-title":"Methods Enzymol."},{"key":"2021111916100832500_BST-2020-1231C89","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1046\/j.1538-7836.2003.00330.x","article-title":"Diverse role of LDL receptor-related protein in the clearance of proteases and in signaling","volume":"1","year":"2003","journal-title":"J. Thromb. Haemost."},{"key":"2021111916100832500_BST-2020-1231C90","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1002\/art.40080","article-title":"Inhibition of shedding of low-density lipoprotein receptor-related protein 1 reverses cartilage matrix degradation in osteoarthritis","volume":"69","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"2021111916100832500_BST-2020-1231C91","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1172\/JCI115262","article-title":"Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity","volume":"87","year":"1991","journal-title":"J. Clin. Invest."},{"key":"2021111916100832500_BST-2020-1231C92","doi-asserted-by":"publisher","first-page":"15810","DOI":"10.1016\/S0021-9258(18)98480-2","article-title":"Kinetics and physiologic relevance of the inactivation of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, and antithrombin III by matrix metalloproteinases-1 (tissue collagenase), -2 (72-kDa gelatinase\/type IV collagenase), and -3 (stromelysin)","volume":"266","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C93","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/S0092-8674(00)00087-8","article-title":"The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B\/MMP-9 in vivo","volume":"102","year":"2000","journal-title":"Cell"},{"key":"2021111916100832500_BST-2020-1231C94","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/S0167-4838(01)00186-8","article-title":"Inactivation of the serpin alpha(2)-antiplasmin by stromelysin-1","volume":"1547","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111916100832500_BST-2020-1231C95","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1002\/art.1780360206","article-title":"Proteolytic inactivation of alpha 1-antitrypsin and alpha 1-antichymotrypsin by neutrophils in arthritic joints","volume":"36","year":"1993","journal-title":"Arthritis Rheum."},{"key":"2021111916100832500_BST-2020-1231C96","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1136\/ard.57.3.162","article-title":"Inactivation of antithrombin III in synovial fluid from patients with rheumatoid arthritis","volume":"57","year":"1998","journal-title":"Ann. Rheum. Dis."},{"key":"2021111916100832500_BST-2020-1231C97","doi-asserted-by":"publisher","first-page":"3931","DOI":"10.1016\/S0021-9258(19)85615-6","article-title":"Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin","volume":"255","year":"1980","journal-title":"J. Biol. Chem."},{"key":"2021111916100832500_BST-2020-1231C98","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1559-0275-11-6","article-title":"Proteomic analysis of human osteoarthritis synovial fluid","volume":"11","year":"2014","journal-title":"Clin. Proteom."},{"key":"2021111916100832500_BST-2020-1231C99","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.joca.2014.12.014","article-title":"Transcriptional analysis of micro-dissected articular cartilage in post-traumatic murine osteoarthritis","volume":"23","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111916100832500_BST-2020-1231C100","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1046\/j.1471-4159.1996.67052039.x","article-title":"Interleukin-1 beta and tumor necrosis factor-alpha induce expression of alpha 1-antichymotrypsin in human astrocytoma cells by activation of nuclear factor-kappa B","volume":"67","year":"1996","journal-title":"J. Neurochem."},{"key":"2021111916100832500_BST-2020-1231C101","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.joca.2004.12.010","article-title":"Elucidation of IL-1\/TGF-beta interactions in mouse chondrocyte cell line by genome-wide gene expression","volume":"13","year":"2005","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111916100832500_BST-2020-1231C102","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/BOR.0000000000000353","article-title":"Role of low-grade inflammation in osteoarthritis","volume":"29","year":"2017","journal-title":"Curr. Opin. Rheumatol."},{"key":"2021111916100832500_BST-2020-1231C103","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.joca.2017.11.015","article-title":"The importance of synovial inflammation in osteoarthritis: current evidence from imaging assessments and clinical trials","volume":"26","year":"2018","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111916100832500_BST-2020-1231C104","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.bbadis.2016.01.003","article-title":"ROS\/oxidative stress signaling in osteoarthritis","volume":"1862","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111916100832500_BST-2020-1231C105","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13075-015-0908-7","article-title":"Targeting oxidative stress to reduce osteoarthritis","volume":"18","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"2021111916100832500_BST-2020-1231C106","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/0049-3848(88)90255-1","article-title":"Oxidative inactivation of purified human alpha-2-antiplasmin, antithrombin III, and C1-inhibitor","volume":"49","year":"1988","journal-title":"Thromb. Res."},{"key":"2021111916100832500_BST-2020-1231C107","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/13813455.2015.1115525","article-title":"Reactive oxygen species and anti-proteinases","volume":"122","year":"2016","journal-title":"Arch. Physiol. Biochem."},{"key":"2021111916100832500_BST-2020-1231C108","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1136\/ard.50.12.915","article-title":"Inactivation of the elastase inhibitory activity of alpha 1 antitrypsin in fresh samples of synovial fluid from patients with rheumatoid arthritis","volume":"50","year":"1991","journal-title":"Ann. Rheum. Dis."},{"key":"2021111916100832500_BST-2020-1231C109","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/0014-5793(93)80123-C","article-title":"Inactivation of synovial fluid alpha 1-antitrypsin by exercise of the inflamed rheumatoid joint","volume":"321","year":"1993","journal-title":"FEBS Lett."},{"key":"2021111916100832500_BST-2020-1231C110","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.1073\/pnas.1713689115","article-title":"Editing out five Serpina1 paralogs to create a mouse model of genetic emphysema","volume":"115","year":"2018","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916100832500_BST-2020-1231C111","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/S0140-6736(15)60860-1","article-title":"Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"2021111916100832500_BST-2020-1231C112","doi-asserted-by":"publisher","first-page":"123","DOI":"10.2147\/JIR.S156405","article-title":"The impact of alpha-1 antitrypsin augmentation therapy on neutrophil-driven respiratory disease in deficient individuals","volume":"11","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"2021111916100832500_BST-2020-1231C113","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s12016-018-8684-1","article-title":"Update on the use of C1-esterase inhibitor replacement therapy in the acute and prophylactic treatment of hereditary angioedema","volume":"56","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"2021111916100832500_BST-2020-1231C114","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1002\/j.1460-2075.1995.tb07299.x","article-title":"Molecular evolution of plasminogen activator inhibitor-1 functional stability","volume":"14","year":"1995","journal-title":"EMBO J."},{"key":"2021111916100832500_BST-2020-1231C115","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1110\/ps.036707.108","article-title":"High-resolution structure of the stable plasminogen activator inhibitor type-1 variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction studies and modeling","volume":"17","year":"2008","journal-title":"Protein Sci."}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/49\/2\/1013\/909852\/bst-2020-1231.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/49\/2\/1013\/909852\/bst-2020-1231.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T16:30:25Z","timestamp":1637339425000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/49\/2\/1013\/228274\/Serpins-in-cartilage-and-osteoarthritis-what-do-we"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,12]]},"references-count":115,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,4,12]]},"published-print":{"date-parts":[[2021,4,30]]}},"URL":"https:\/\/doi.org\/10.1042\/bst20201231","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,12]]}}}