{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:08:24Z","timestamp":1792458504061,"version":"4.5.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,8,28]]},"abstract":"<jats:p>\n                    The Wnt antagonist Sost has emerged as a key regulator of bone homeostasis through the modulation of Lrp4\/5\/6 Wnt coreceptors. In humans, lack of Sclerostin causes sclerosteosis and van Buchem (VB) disease, two generalized skeletal hyperostosis disorders that result from hyperactive Wnt signaling. Unlike sclerosteosis, VB patients lack\n                    <jats:italic>SOST<\/jats:italic>\n                    coding mutations but carry a homozygous 52 kb noncoding deletion that is essential for the transcriptional activation of\n                    <jats:italic>SOST<\/jats:italic>\n                    in bone. We recently identified a putative bone enhancer,\n                    <jats:italic>ECR5<\/jats:italic>\n                    , in the VB deletion region, and showed that the transcriptional activity of\n                    <jats:italic>ECR5<\/jats:italic>\n                    is controlled by Mef2C transcription factor in vitro. Here we report that mice lacking\n                    <jats:italic>ECR5<\/jats:italic>\n                    or\n                    <jats:italic>Mef2C<\/jats:italic>\n                    through\n                    <jats:italic>Col1-Cre<\/jats:italic>\n                    osteoblast\/osteocyte-specific ablation result in high bone mass (HBM) due to elevated bone formation rates. We conclude that the absence of the\n                    <jats:italic>Sost<\/jats:italic>\n                    -specific long-range regulatory element\n                    <jats:italic>ECR5<\/jats:italic>\n                    causes VB disease in rodents, and that Mef2C is the main transcription factor responsible for\n                    <jats:italic>ECR5<\/jats:italic>\n                    -dependent\n                    <jats:italic>Sost<\/jats:italic>\n                    transcriptional activation in the adult skeleton.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1207188109","type":"journal-article","created":{"date-parts":[[2012,8,11]],"date-time":"2012-08-11T22:24:53Z","timestamp":1344723893000},"page":"14092-14097","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":132,"title":["Targeted deletion of\n                    <i>Sost<\/i>\n                    distal enhancer increases bone formation and bone mass"],"prefix":"10.1073","volume":"109","author":[{"given":"Nicole M.","family":"Collette","sequence":"first","affiliation":[{"name":"Physical and Life Sciences Directorate, Lawrence Livermore National Laboratories, Livermore, CA 94550;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian C.","family":"Genetos","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris N.","family":"Economides","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Tarrytown, NY 10591;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiQin","family":"Xie","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Tarrytown, NY 10591;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Shahnazari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA 95817;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA 95817;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy E.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA 95817;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Harland","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; 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