{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:07:25Z","timestamp":1789016845481,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MEXT KAKENHI","award":["JP16K11443"],"award-info":[{"award-number":["JP16K11443"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We recently reported an unexpected role of osteoblast-derived matrix vesicles in the delivery of microRNAs to bone matrix. Of such microRNAs, we found that miR-125b inhibited osteoclast formation by targeting Prdm1 encoding a transcriptional repressor of anti-osteoclastogenesis factors. Transgenic (Tg) mice overexpressing miR-125b in osteoblasts by using human osteocalcin promoter grow normally but exhibit high trabecular bone mass. We have now further investigated the effects of osteoblast-mediated miR-125b overexpression on skeletal morphogenesis and remodeling during development, aging and in a situation of skeletal repair, i.e., fracture healing. There were no significant differences in the growth plate, primary spongiosa or lateral (periosteal) bone formation and mineral apposition rate between Tg and wild-type (WT) mice during early bone development. However, osteoclast number and medial (endosteal) bone resorption were less in Tg compared to WT mice, concomitant with increased trabecular bone mass. Tg mice were less susceptible to age-dependent changes in bone mass, phosphate\/amide I ratio and mechanical strength. In a femoral fracture model, callus formation progressed similarly in Tg and WT mice, but callus resorption was delayed, reflecting the decreased osteoclast numbers associated with the Tg callus. These results indicate that the decreased osteoclastogenesis mediated by miR-125b overexpression in osteoblasts leads to increased bone mass and strength, while preserving bone formation and quality. They also suggest that, in spite of the fact that single miRNAs may target multiple genes, the miR-125b axis may be an attractive therapeutic target for bone loss in various age groups.<\/jats:p>","DOI":"10.3390\/ijms22136745","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T11:28:41Z","timestamp":1624447721000},"page":"6745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Overexpression of miR-125b in Osteoblasts Improves Age-Related Changes in Bone Mass and Quality through Suppression of Osteoclast Formation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1907-9324","authenticated-orcid":false,"given":"Shota","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Calcified Tissue Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Minami-ku, Hiroshima 734-8553, Japan"},{"name":"Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Minamizaki","sequence":"additional","affiliation":[{"name":"Department of Calcified Tissue Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Kohno","sequence":"additional","affiliation":[{"name":"Department of Calcified Tissue Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Sotomaru","sequence":"additional","affiliation":[{"name":"Natural Science Center for Basic Research and Development, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kitaura","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, The University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Ohba","sequence":"additional","affiliation":[{"name":"Department of Sensory and Motor System Medicine, The University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshie","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Niigata University Graduate School of Science and Technology, Nishi-ku, Niigata 950-2181, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Aubin","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, 1 King\u2019s College Circle, Medical Sciences Building, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Yoshiko","sequence":"additional","affiliation":[{"name":"Department of Calcified Tissue Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Minami-ku, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1126\/science.1064921","article-title":"Identification of Novel Genes Coding for Small Expressed RNAs","volume":"294","year":"2001","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/ncb0309-228","article-title":"Many Roads to Maturity: MicroRNA Biogenesis Pathways and Their Regulation","volume":"11","author":"Winter","year":"2009","journal-title":"Nat. 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