{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:51:28Z","timestamp":1790265088893,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,8,26]],"date-time":"2004-08-26T00:00:00Z","timestamp":1093478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica Scandinavica"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Aims:\u2002<\/jats:bold> Insulin\u2010like growth factor\u2010I (IGF\u2010I), parathyroid hormone (PTH) and PTH\u2010related protein (PTHrP) are hormones that have anabolic effects on bone formation. The aim of this study was to investigate whether production of nitric oxide (NO) is involved in the effect of IGF\u2010I and PTH\/PTHrP on osteoblast\u2010like cells.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Bone marrow stromal cells from adult endothelial nitric oxide synthase (eNOS)\u2010knockout (eNOSKO) mice and wild type (WT) counterparts were cultivated with osteogenic substances. The cells showed an osteoblastic phenotype measured as osteocalcin production and alkaline phosphatase activity. DNA synthesis was measured as [<jats:sup>3<\/jats:sup>H] thymidine incorporation in the bone marrow cells and in a human osteosarcoma cell\u2010line (SaOS\u20102).<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> The stimulatory effect of IGF\u2010I on thymidine incorporation seen in WT animals was absent in eNOSKO mice. Addition of a NO donor to eNOSKO cells recovered the effect of IGF\u2010I on thymidine incorporation. PTH\/PTHrP stimulated cell proliferation in both WT and eNOSKO mice. In SaOS\u20102 cells, incubation with IGF\u2010I together with a NOS inhibitor resulted in an inhibition of the anabolic effect of IGF\u2010I on cell proliferation.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> The stimulatory effect of IGF\u2010I on WT cell proliferation was abolished in eNOSKO cells, recovered by an NO donor and inhibited in osteosarcoma cells by a NOS inhibitor. The results indicate that the effect of IGF\u2010I is dependent on NO production. The impaired IGF\u2010I response may contribute to the bone defect formation seen in eNOSKO animals.<\/jats:p>","DOI":"10.1111\/j.1365-201x.2004.01303.x","type":"journal-article","created":{"date-parts":[[2004,8,26]],"date-time":"2004-08-26T08:41:59Z","timestamp":1093509719000},"page":"29-35","source":"Crossref","is-referenced-by-count":29,"title":["Inhibited anabolic effect of insulin\u2010like growth factor\u2010I on stromal bone marrow cells in endothelial nitric oxide synthase\u2010knockout 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