{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T07:04:38Z","timestamp":1780988678893,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Osteoclasts derived from hematopoietic stem cells control bone resorption. Identifying novel molecules that can epigenetically regulate osteoclastogenesis is important for developing novel treatments for osteoporosis and other disorders associated with bone deterioration and promoting healthy bone formation. The polycomb group (PcG) protein enhancer of zeste homolog 2 (Ezh2), a histone lysine methyltransferase, is associated with epigenetic regulation of numerous cellular processes, but its involvement in bone cell development and homeostasis is not yet clear. Here, LysM\u2010Cre mice were crossed with Ezh2\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    mice to delete Ezh2 in myeloid cell lineage mature macrophages. Conditional knockout of\n                    <jats:italic>Ezh2<\/jats:italic>\n                    (CKO) in myeloid cell line resulted in significant increases in postnatal bone growth in the first 6\u2009months of life for both male and female mice. For female mice, optimal bone mass was seen for mice with\n                    <jats:italic>Ezh2<\/jats:italic>\n                    deleted in both chromosomes in a pair (f\/f Cre\n                    <jats:sup>+<\/jats:sup>\n                    ; CKO). For male mice, optimal bone mass was found after deletion of\n                    <jats:italic>Ezh2<\/jats:italic>\n                    from just one chromosome (f\/\u2212 Cre\n                    <jats:sup>+<\/jats:sup>\n                    ) with no difference in bone phenotype between f\/\u2212 Cre\n                    <jats:sup>+<\/jats:sup>\n                    and CKO male mice. In addition to the gender\u2010specific difference in bone phenotype,\n                    <jats:italic>Ezh2<\/jats:italic>\n                    CKO mice had significantly less macrophages (CD11b+) present in the bone marrow compared with control mice as well as significantly more mature osteoblasts and bone formation biomarkers present (P1NP, osteocalcin). Inflammatory array for protein lysed from bone tissue revealed deletion of\n                    <jats:italic>Ezh2<\/jats:italic>\n                    decreased inflammatory milieu in both male and female mice compared with controls. Unexpectedly, myeloid cell deletion of Ezh2 also increased the number of mature osteoblast present in the bone. Deletion of\n                    <jats:italic>Ezh2<\/jats:italic>\n                    also led to an increase in gene expression of osteoclast\u2010suppressive genes\n                    <jats:italic>IRF8<\/jats:italic>\n                    ,\n                    <jats:italic>MafB,<\/jats:italic>\n                    and\n                    <jats:italic>Arg1<\/jats:italic>\n                    due to a decrease in the presence of the suppressive H3K27me3 epigenetic mark. These findings suggest that manipulation of Ezh2 expression may be a viable strategy to combat bone resorptive disorders such as osteoporosis or arthritis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201673rr","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T17:46:33Z","timestamp":1686159993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Decreased bone resorption in Ezh2 myeloid cell conditional knockout mouse model"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2977-271X","authenticated-orcid":false,"given":"Perry C.","family":"Caviness","sequence":"first","affiliation":[{"name":"Arkansas Children's Nutrition Center  Little Rock Arkansas USA"},{"name":"Department of Pediatrics University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongzheng","family":"Gai","sequence":"additional","affiliation":[{"name":"Myeloma Center University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oxana P.","family":"Lazarenko","sequence":"additional","affiliation":[{"name":"Arkansas Children's Nutrition Center  Little Rock Arkansas USA"},{"name":"Department of Pediatrics University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Arkansas Children's Nutrition Center  Little Rock Arkansas USA"},{"name":"Department of Pediatrics University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghuang","family":"Zhan","sequence":"additional","affiliation":[{"name":"Myeloma Center University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Ran","family":"Chen","sequence":"additional","affiliation":[{"name":"Arkansas Children's Nutrition Center  Little Rock Arkansas USA"},{"name":"Department of Pediatrics University of Arkansas for Medical Sciences  Little Rock Arkansas 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