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Whereas most research efforts in recent years have investigated the pathologies associated with MMP-2 overactivity, the pathological mechanisms elicited by MMP-2 underactivity are less well understood. Here, we distinguish between 2 states and describe their causes: (i) MMP-2 deficiency (complete loss of MMP-2 activity) and (ii) MMP-2 insufficiency (defined as MMP-2 activity below baseline levels). Further, we review the biology of MMP-2, summarizing the current literature on MMP-2 underactivity in both mice and humans, and describe research being conducted by our lab towards improving our understanding of the pathological mechanisms elicited by MMP-2 deficiency\/insufficiency. We think that this research could stimulate the discovery of new therapeutic approaches for managing pathologies associated with MMP-2 underactivity. Moreover, similar concepts could apply to other members of the matrix metalloproteinase family. <\/jats:p>","DOI":"10.1139\/cjpp-2018-0525","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T21:42:07Z","timestamp":1542750127000},"page":"486-492","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Pathologies of matrix metalloproteinase-2 underactivity: a perspective on a neglected condition"],"prefix":"10.1139","volume":"97","author":[{"given":"Ryan","family":"Cook","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, 3-19 Medical Sciences Building, University of Alberta, Edmonton, AB T6G 2H7, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Sarker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine and Dentistry, 3-19 Medical Sciences Building, University of Alberta, Edmonton, AB T6G 2H7, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Fernandez-Patron","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, 3-19 Medical Sciences Building, University of Alberta, Edmonton, AB T6G 2H7, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-325225"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.035725"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.7.4858"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133928"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)80056-0"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.001868"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37447"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80312-I"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800054-JLR200"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2014.0581"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-013-2102-8"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900273200"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1038\/ni773"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.1021\/bi00252a007"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-011-0290-8"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00018.x"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.1586\/erm.09.28"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0757.2000.2230103.x"},{"key":"refg20\/ref20","doi-asserted-by":"publisher","DOI":"10.4274\/Jcrpe.1166"},{"key":"refg21\/ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.022"},{"key":"refg22\/ref22","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.17.5238"},{"key":"refg23\/ref23","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c160010"},{"key":"refg24\/ref24","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-007-0654-6"},{"key":"refg25\/ref25","doi-asserted-by":"publisher","DOI":"10.1186\/ar79"},{"issue":"2","key":"refg26\/ref26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1600-051X.1995.tb00120.x","volume":"22","author":"Golub L.M.","year":"1995","journal-title":"J. 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