Low-dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent osteopenic mice

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   Figure 1

   Distinct effects of standard and low-dose intermittent PTH on bone mass and microarchitecture in prematurely senescent osteopenic Samp6 mice. Representative microCT images of lumbar vertebrae (A) showing that both doses of PTH increased bone mass in Samp6 mice. (B, C, D and E) Analysis of bone microarchitecture parameters showing the distinct effects of PTH at the standard and low doses on bone volume (BV, expressed relative to trabecular volume (TV)), trabecular thickness (Tb. Th), trabecular number (Tb. No) and trabecular separation (Tb. Sep). Mean±s.d. of six to eight mice. *Statistically significant (P<0.05).
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   Figure 2

   Histomorphometric analysis showing that intermittent low-dose PTH increased trabecular bone volume (A and B) and trabecular bone thickness (C) but not trabecular number (D) or separation (E) in vertebral bone in prematurely senescent osteopenic Samp6 mice. Mean±s.d. of six to eight mice. *Statistically significant (P<0.05).
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   Figure 3

   Intermittent PTH at low and standard doses increased serum P1NP levels in prematurely senescent osteopenic Samp6 mice after 6 weeks of treatment. Mean±s.d. of six to eight mice. *Statistically significant (P<0.05).
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   Figure 4

   Intermittent low-dose PTH increased osteoblast activity but not bone forming surface in the vertebrae of prematurely senescent osteopenic Samp6 mice. Low-dose PTH had no effect double-labelled surface (DLS) (A) or bone formation rate (BFR) (C) but increased the mineral apposition rate (MAR) (B). Mean±s.d. of six to eight mice. *Statistically significant (P<0.05).
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   Figure 5

   Intermittent low-dose PTH increased expression of the osteoblast differentiation markers Alp (A), Col1a1 (B) and Oc (C) in prematurely senescent osteopenic Samp6 mice. Quantitative RT-PCR analysis of osteoblast gene expression was carried out in the bone marrow stromal cells and osteoblasts/osteocytes extracted from long bones in control Samp6 mice or mice treated with low-dose PTH for 6 weeks. The transcript levels were normalized to the values for HPRT. Mean±s.d. of six to eight mice. *Statistically significant (P<0.05).
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   Figure 6

   Intermittent low-dose PTH modulated Wnt signalling effectors Wisp1 (A), Sost (B) and Mef2c (C) in prematurely senescent osteopenic Samp6 mice. Quantitative RT-PCR analysis of Wnt effectors was carried out using bone marrow stromal cells and osteoblasts/osteocytes extracted from long bones (or pooled populations for Mef2c) of control Samp6 mice or mice treated with PTH at a low dose for 6 weeks. The transcript levels were normalized to the values for HPRT. Mean±s.d. of six to eight mice. *Statistically significant (P<0.05).
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   Figure 7

   Proposed mechanism of the anabolic effect of low-dose PTH in prematurely senescent osteopenic Samp6 mice. Low-dose PTH increased osteoblast activity, but not number, by modulating specific Wnt effectors, resulting in increased bone formation and axial bone volume in senescent osteopenic Samp6 mice.

• © 2014 Society for Endocrinology