{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:59:00Z","timestamp":1792709940109,"version":"4.5.0"},"reference-count":31,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p>\n                    Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like growth factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Yet,\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8- and 16-week-old\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Both male and female adult\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks. Marked reductions in aBMD and aBMC were observed in 16-week-old\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    females, but not in males. Femoral trabecular BV\/TV and thickness, cortical fraction and thickness in 16-week-old\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    females were significantly reduced. However, surprisingly, males had significantly more trabeculae with higher connectivity density than controls. Concordantly, histomorphometry revealed higher bone resorption and lower bone formation in\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    females. In contrast,\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    males had lower mineralized surface\/bone surface. Femoral expression of\n                    <jats:italic>Sost<\/jats:italic>\n                    and circulating levels of sclerostin were reduced but only in\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    males. Bone marrow stromal cultures from mutants showed increased osteogenesis, whereas osteoclastogenesis was markedly increased in cells from\n                    <jats:italic>\n                      Igfbp4\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    females but decreased in males. In sum, our results indicate that loss of\n                    <jats:italic>Igfbp4<\/jats:italic>\n                    affects mesenchymal stromal cell differentiation, regulates osteoclastogenesis and influences both skeletal development and adult bone maintenance. Thus, IGFBP-4 modulates the skeleton in a gender-specific manner, acting as both a cell autonomous and cell non-autonomous factor.\n                  <\/jats:p>","DOI":"10.1530\/joe-16-0673","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T20:25:20Z","timestamp":1486671920000},"page":"131-144","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":45,"title":["IGFBP-4 regulates adult skeletal growth in a sex-specific manner"],"prefix":"10.1530","volume":"233","author":[{"given":"David E","family":"Maridas","sequence":"first","affiliation":[{"name":"1Maine Medical Center Research InstituteScarborough, Maine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E","family":"DeMambro","sequence":"additional","affiliation":[{"name":"1Maine Medical Center Research InstituteScarborough, Maine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong 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