{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:13:11Z","timestamp":1783548791617,"version":"3.55.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2011,5,16]],"date-time":"2011-05-16T00:00:00Z","timestamp":1305504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Parathyroid hormone (PTH) is widely recognized as a key regulator of mineral ion homeostasis. Daily intermittent administration of PTH is the only currently available anabolic therapy for bone disorders such as osteoporosis. Recent studies have shown that PTH increases transcription and secretion of fibroblast growth factor 23 (FGF-23), another important regulator of phosphate homeostasis and skeletal metabolism. However, the full relationship between PTH and FGF-23 is largely unknown. This study evaluated the effect of FGF-23\/Klotho signaling on the phosphaturic and anabolic functions of PTH. Eight-day-old wild-type (WT) Fgf23\u2212\/\u2212 and Kl\u2212\/\u2212 mice were injected with 100\u2009\u00b5g\/kg PTH(1\u201334) or vehicle daily for a 2-week-period and then euthanized. Intermittent injection of PTH successfully reduced the serum phosphate levels and reversed the hyperphosphatemia of Fgf23\u2212\/\u2212 and Kl\u2212\/\u2212 mice. Bone changes were analyzed in the distal femur metaphysis by peripheral quantitative computed tomography (pQCT), micro\u2013computed tomography (\u00b5CT), and histomorphometry. PTH treatment induced substantial increases in bone mineral density (BMD) and trabecular bone volume in each mouse genotype. Expression of osteoblastic marker genes, including Runx2, Col1, Alp, Ocn, and Sost, was similarly altered. In addition, primary osteoblasts were isolated and treated with 100\u2009nM PTH in vitro. PTH treatment similarly induced cAMP accumulation and phosphorylation of ERK1\/2 and CREB in the osteoblasts from each genotype. Taken together, our results demonstrate that FGF-23\/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH, suggesting that PTH can function as a therapeutic agent to improve the skeletal quality of patients even in the presence of abnormal serum FGF-23 levels. \u00a9 2011 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.433","type":"journal-article","created":{"date-parts":[[2011,5,16]],"date-time":"2011-05-16T16:20:12Z","timestamp":1305562812000},"page":"2026-2035","source":"Crossref","is-referenced-by-count":49,"title":["FGF-23\/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH"],"prefix":"10.1093","volume":"26","author":[{"given":"Quan","family":"Yuan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, People's Republic of China"},{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadatoshi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Densmore","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Sch\u00fcler","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold G","family":"Erben","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Lanske","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,16]]},"reference":[{"key":"2024020317574366400_bib1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1677\/joe.1.06057","article-title":"Parathyroid hormone: past and present","volume":"187","author":"Potts","year":"2005","journal-title":"J 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