{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:04:33Z","timestamp":1789185873027,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,16]],"date-time":"2018-02-16T00:00:00Z","timestamp":1518739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["26293332, 17K11000"],"award-info":[{"award-number":["26293332, 17K11000"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Osteoporosis is a progressive bone disease caused by an imbalance between bone resorption and formation. Recently, plasminogen activator inhibitor\u20101 (<jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content>\u20101) was shown to play an important role in bone metabolism using <jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content>\u20101\u2010deficient mice. In this study, we evaluated the therapeutic benefits of novel, orally available small\u2010molecule PAI\u20101 inhibitor (<jats:styled-content style=\"fixed-case\">iPAI<\/jats:styled-content>\u20101) in an estrogen deficiency\u2010induced osteoporosis model. Eight\u2010week\u2010old C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J female mice were divided into three groups: a sham\u00a0+\u00a0vehicle (Sham), ovariectomy\u00a0+\u00a0vehicle (<jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u00a0+\u00a0v), and <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">iPAI<\/jats:styled-content>\u20101 (<jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u00a0+\u00a0i) group. <jats:styled-content style=\"fixed-case\">iPAI<\/jats:styled-content>\u20101 was administered orally each day for 6\u00a0weeks starting the day after the operation. Six weeks of <jats:styled-content style=\"fixed-case\">iPAI<\/jats:styled-content>\u20101 treatment prevented <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u2010induced trabecular bone loss in both the femoral bone and lumbar spine. Bone formation activity was significantly higher in the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u00a0+\u00a0i group than in the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u00a0+\u00a0v and Sham groups. Unexpectedly, <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u2010induced osteoclastogenesis was partially, but significantly reduced. Fluorescence\u2010activated cell sorting analyses indicated that the number of bone marrow stromal cells was higher in the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u00a0+\u00a0i group than that in the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u00a0+\u00a0v group. A colony\u2010forming unit\u2010osteoblast assay indicated enhanced mineralized nodule formation activity in bone marrow cells isolated from <jats:styled-content style=\"fixed-case\">iPAI<\/jats:styled-content>\u20101\u2010treated animals. Bone marrow ablation analysis indicated that the remodeled trabecular bone volume was significantly higher in the <jats:styled-content style=\"fixed-case\">iPAI<\/jats:styled-content>\u20101\u2010treated group than that in the control group. In conclusion, our results suggest <jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content>\u20101 blockade via a small\u2010molecule inhibitor is a new therapeutic approach for the anabolic treatment of postmenopausal osteoporosis.<\/jats:p>","DOI":"10.1002\/2211-5463.12390","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T14:36:42Z","timestamp":1516804602000},"page":"523-532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A small\u2010molecule <scp>PAI<\/scp>\u20101 inhibitor prevents bone loss by stimulating bone formation in a murine estrogen deficiency\u2010induced osteoporosis model"],"prefix":"10.1002","volume":"8","author":[{"given":"Guangwen","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Orthopedics Surgery Tokyo Medical and Dental University Japan"},{"name":"Department of Orthopaedic Surgery Yanbian University Hospital Yanji 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