{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:18:55Z","timestamp":1791847135071,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,11,30]],"date-time":"2010-11-30T00:00:00Z","timestamp":1291075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Infrastructure Grant from the Michael Smith Research Foundation to the University of British Columbia Centre for Blood Research"},{"DOI":"10.13039\/501100000245","name":"Michael Smith Foundation for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Canadian Institutes of Health Research Strategic Training Program","award":["STP-53877"],"award-info":[{"award-number":["STP-53877"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Neutrophil accumulation is balanced by both cell infiltration and cell clearance, the controls of which are pivotal in the pathogenesis of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Of the neutrophil\u2010specific proteases, matrix metalloproteinase 8 (MMP\u20108; also known as neutrophil collagenase or collagenase 2) is traditionally viewed as being crucial for collagen degradation and hence cell migration and infiltration. This study was undertaken to examine the role of MMP\u20108 in a murine model of spontaneous RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      MMP\u20108\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were backcrossed onto the Fas\u2010defective MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      background, a mouse strain characterized by systemic autoimmunity including spontaneous autoimmune arthritis. Arthritis was induced with Freund's complete adjuvant and clinical disease and histologic parameters were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MMP\u20108\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice had earlier and more severe joint inflammation than their MMP\u20108\n                      <jats:sup>+\/+<\/jats:sup>\n                      counterparts, coupled with a massive accumulation of neutrophils in synovial tissue, an unexpected result considering the commonly held view that MMP\u20108 has important extracellular matrix\u2013degradative functions. Protease and protease inhibitor analysis of MMP\u20108\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mouse neutrophils by CLIP\u2010CHIP microarray revealed very little additional change in protease levels except for low expression of the apoptosis initiator caspase 11. This was confirmed at the protein level in unstimulated, lipopolysaccharide\u2010treated, and interferon\u2010\u03b3\u2013treated MMP\u20108\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mouse neutrophils. Downstream of caspase 11, the activity of the apoptosis executioner caspase 3 was consequently reduced in MMP\u20108\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mouse neutrophils, translating to reduced neutrophil apoptosis and cell accumulation compared with wild\u2010type mouse cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that MMP\u20108 is not essential for neutrophil migration in arthritis and likely other autoimmune diseases. Rather, MMP\u20108 is important for normal rates of neutrophil apoptosis and hence regulates cell clearance. Because MMP\u20108 deficiency leads to an exaggerated accumulation of neutrophil infiltrates due to delayed apoptosis and concurrent pathologic changes associated with dramatically increased neutrophil infiltration, MMP\u20108 is antiinflammatory and therefore a drug antitarget in the treatment of arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.27757","type":"journal-article","created":{"date-parts":[[2010,11,30]],"date-time":"2010-11-30T14:35:56Z","timestamp":1291127756000},"page":"3645-3655","source":"Crossref","is-referenced-by-count":68,"title":["Matrix metalloproteinase 8 deficiency in mice exacerbates inflammatory arthritis through delayed neutrophil apoptosis and reduced caspase 11 expression"],"prefix":"10.1002","volume":"62","author":[{"given":"Jennifer H.","family":"Cox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda 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