Search Results
You are looking at 1 - 1 of 1 items for
- Author: Pierre J Marie x
- Refine by access: All content x
UMR‐1132 Inserm, Université Paris Diderot, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France
Search for other papers by Zuzana Saidak in
Google Scholar
PubMed
UMR‐1132 Inserm, Université Paris Diderot, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France
Search for other papers by Carole Le Henaff in
Google Scholar
PubMed
UMR‐1132 Inserm, Université Paris Diderot, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France
Search for other papers by Sofia Azzi in
Google Scholar
PubMed
UMR‐1132 Inserm, Université Paris Diderot, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France
Search for other papers by Caroline Marty in
Google Scholar
PubMed
UMR‐1132 Inserm, Université Paris Diderot, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France
Search for other papers by Pierre J Marie in
Google Scholar
PubMed
Intermittent administration of parathyroid hormone (PTH) 1–34 at a standard dose has been shown to induce anabolic effects in bone. However, whether low-dose PTH promotes bone formation during senescence is unknown. To address this issue, we determined the effects of low-dose PTH and analysed the underlying mechanisms in prematurely senescent mice that display osteopenia. Treatment of 9-week-old Samp6 mice for 6 weeks with PTH at a standard dose (100 μg/kg per day) increased vertebral and femoral bone mass and improved bone microarchitecture as a result of increased bone-forming surfaces and mineral apposition rate (MAR). At a tenfold lower dose (10 μg/kg per day), PTH increased axial bone volume and trabecular thickness, as detected by bone histomorphometry but not by micro-computed tomography analysis. This anabolic effect resulted from increased osteoblast activity, as reflected by increased serum N-terminal propeptide of type 1 procollagen (P1NP) levels and MAR, with unchanged bone-forming surface or osteoblast surface. Mechanistically, low-dose PTH increased the expression of osteoblast markers in bone marrow stromal cells and mature osteoblasts, which was associated with increased expression of the Wnt effector Wisp1. Moreover, low-dose PTH decreased the expression of the Mef2c transcription factor, resulting in decreased Sost expression in osteoblasts/osteocytes. These results indicate that PTH at a low dose is effective at promoting bone formation and increased bone volume in senescent osteopenic mice through increased osteoblast activity and modulation of specific Wnt effectors, which raises the potential therapeutic use of intermittent PTH at low dose to increase bone forming activity and bone mass in skeletal senescence.
