title: FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH.
abstract: 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(-/-) and Kl(-/-) mice were injected with 100 µg/kg PTH(1-34) 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(-/-) and Kl(-/-) mice. Bone changes were analyzed in the distal femur metaphysis by peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT), 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 nM 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.
authors: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors: Quan
authors: Q
authors: Yuan
authors: Tadatoshi
authors: T
authors: Sato
authors: Michael
authors: M
authors: Densmore
authors: Hiroaki
authors: H
authors: Saito
authors: Christiane
authors: C
authors: Schüler
authors: Reinhold G
authors: RG
authors: Erben
authors: Beate
authors: B
authors: Lanske
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