{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:48:19Z","timestamp":1773287299468,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T00:00:00Z","timestamp":1248739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The osteo\u2010anabolic effects of intermittent parathyroid hormone (PTH) treatment require insulin\u2010like growth factor (IGF) signaling through the IGF\u2010I receptor. A major downstream target of the IGF\u2010I receptor (via Akt) is the mammalian target of rapamycin (mTOR), a kinase involved in protein synthesis. We investigated whether the bone\u2010building effects of intermittent PTH require functional mTOR signaling. Mice were treated with daily PTH 1\u201334 (0, 10, 30, or 90\u2009\u00b5g\/kg) for 6 weeks in the presence or absence of rapamycin, a selective inhibitor of mTOR. We found that all PTH doses were effective in enhancing bone mass, whether rapamycin was present or not. Rapamycin had little to no effect on the anabolic response at low (10\u2009\u00b5g) PTH doses, small effects in a minority of anabolic measures at moderate doses (30\u2009\u00b5g), but the anabolic effects of high\u2010dose PTH (90\u2009\u00b5g) were consistently and significantly suppressed by rapamycin (\u223c4\u201336% reduction). Serum levels of Trap5b, a marker of resorption, were significantly enhanced by rapamycin, but these effects were observed whether PTH was absent or present. Our data suggest that intermittent PTH, particularly at lower doses, is effective in building bone mass in the presence of rapamycin. However, the full anabolic effects of higher doses of PTH are significantly suppressed by rapamycin, suggesting that PTH might normally activate additional pathways (including mTOR) for its enhanced high\u2010dose anabolic effects. Clinical doses of intermittent PTH could be an effective treatment for maintaining or increasing bone mass among patients taking rapamycin analogs for unrelated health issues. J. Cell. Physiol. 221: 579\u2013585, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21887","type":"journal-article","created":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T21:48:55Z","timestamp":1248817735000},"page":"579-585","source":"Crossref","is-referenced-by-count":13,"title":["Rapamycin impairs trabecular bone acquisition from high\u2010dose but not low\u2010dose intermittent parathyroid hormone treatment"],"prefix":"10.1002","volume":"221","author":[{"given":"P.J.","family":"Niziolek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Murthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.N.","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.B.","family":"Sukhija","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.A.","family":"Hornberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.H.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.G.","family":"Robling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,9,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.9.1570"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.1.72"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1212704"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20671"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01352014"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02480-6"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000150332.42276.69"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10490"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00636-6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209888"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.009"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105103441904"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709909200"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2494"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650100513"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601000200"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21411"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042831"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.04.012"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2008.11.004"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.12-8-1007"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070517"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.55.091902.105243"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.016"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1511"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.21887","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.21887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T19:26:09Z","timestamp":1696793169000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.21887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,25]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1002\/jcp.21887"],"URL":"https:\/\/doi.org\/10.1002\/jcp.21887","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,25]]}}}