scholarly journals Pretreatment with Anticatabolic Agents Blunts But Does Not Eliminate the Skeletal Anabolic Response to Parathyroid Hormone in Oophorectomized Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2778-2787 ◽  
Author(s):  
Rana Samadfam ◽  
Qingwen Xia ◽  
David Goltzman
Keyword(s):  
Parathyroid Hormone ◽  
Anabolic Response

scholarly journals EphrinB2/EphB4 inhibition in the osteoblast lineage modifies the anabolic response to parathyroid hormone

2013 ◽  
Vol 28 (4) ◽  
pp. 912-925 ◽  
Author(s):  
Farzin M Takyar ◽  
Stephen Tonna ◽  
Patricia WM Ho ◽  
Blessing Crimeen-Irwin ◽  
Emma K Baker ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Anabolic Response ◽  
Osteoblast Lineage

scholarly journals Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43

2006 ◽  
Vol 119 (20) ◽  
pp. 4187-4198 ◽  
Author(s):  
D. J. Chung ◽  
C. H. M. Castro ◽  
M. Watkins ◽  
J. P. Stains ◽  
M. Y. Chung ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Mass ◽  
Peak Bone Mass ◽  
Anabolic Response ◽  
Specific Deletion

Impaired bone anabolic response to parathyroid hormone in Fgf2−/− and Fgf2+/− mice

2006 ◽  
Vol 341 (4) ◽  
pp. 989-994 ◽  
Author(s):  
M.M. Hurley ◽  
Y. Okada ◽  
L. Xiao ◽  
Y. Tanaka ◽  
M. Ito ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Anabolic Response

scholarly journals SAT-392 The Role of β-arrestin2 in Bone Catabolic Response to Hyperparathyroidism In Vivo

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Gilberto Li Feng ◽  
Marc Grynpas ◽  
Jane Mitchell
Keyword(s):  
Parathyroid Hormone ◽  
Trabecular Bone ◽  
Histological Analysis ◽  
Bone Microarchitecture ◽  
Biomechanical Testing ◽  
Micro Computed Tomography ◽  
Anabolic Response ◽  
Protein Levels ◽  
Dynamic Histomorphometry

Abstract Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by elevated parathyroid hormone (PTH) levels and hypercalcemia caused by the overactive parathyroid glands, resulting in negative impacts on the skeleton including bone loss and increased bone fragility1. PTH binds and activates parathyroid hormone type 1 receptor (PTH1R) which primary couples to Gαs, stimulating the downstream effectors that mediate bone remodeling processes2. PTH1R activity is regulated by arrestins, specially β-arrestin2 (β-arr2), through signal termination and receptor internalization2. Previously, we have seen anabolic effects of hyperparathyroidism (cPTH) on trabecular bone in mice overexpressing Gαs3. We hypothesized that increased Gαs protein levels in osteoblasts outcompete β-arr binding to PTH1R, leading to reduced signal termination and increased bone formation. To test this hypothesis, we are testing if the deletion of β-arr2 will also result in an anabolic response to cPTH in this study. The response of β-arr2 knockout (KO) mice to cPTH have yet to be documented. The hypothesis of this study is that β-arr2 KO mice treated with cPTH will exhibit anabolic effects on the trabecular bone. Nine-week-old wild-type (WT) C57BL/6 and β-arr2 KO mice were treated for 14 days with either rPTH1-34 (80ng/g/day) or saline (PBS) using micro-osmotic pumps to simulate hyperparathyroidism. There are 8 groups (n=10 per group) including both sexes, 2 genotypes (WT and KO), and 2 treatment groups (PTH and PBS). Two 30 mg/kg doses of 0.6% calcein green were administered subcutaneously to mice at 7 and 2 days prior to euthanasia to label bones. Decalcified tibiae were embedded in paraffin for histological analysis. Undecalcified tibiae were embedded in plastic for dynamic histomorphometry. Micro-computed tomography (μCT) was used to access bone microarchitecture of femurs and vertebrae followed by biomechanical testing of bone strength. The μCT data of distal femurs show that cPTH treatment increased bone volume in female KO mice (6.864 ± 2.318 vs 4.690 ± 1.555 %; P= 0.0328; n=9 per group) and maintained bone in male KO mice (13.37 ± 2.860 vs 13.38 ± 3.135; P= 0.9968, n= 10) compared to control. Histological analysis show higher osteoclastic activity in both sexes and genotypes when treated with cPTH, suggesting that the anabolic response may be at the level of osteoblasts and osteocytes. These promising results support our hypothesis that arrestin-mediated PTH receptor downregulation plays an importance role in bone weakness associated with hyperparathyroidism. These studies are important for understanding the clinical phenotype of PHPT patients and suggest that inhibition of β-arr2 in PHPT could be a path for drug therapy. References: (1) Mosekilde L. Clin Endocrinol 2008;69:1-9. (2) Ferrari SL et al., J Biol Chem 1999; 274:29968–29975 (3) Zhang L. PhD thesis University of Toronto, 2018.

scholarly journals Are Osteoclasts Needed for the Bone Anabolic Response to Parathyroid Hormone?

2010 ◽  
Vol 285 (36) ◽  
pp. 28164-28173 ◽  
Author(s):  
Dominique D. Pierroz ◽  
Nicolas Bonnet ◽  
Paul A. Baldock ◽  
Michael S. Ominsky ◽  
Marina Stolina ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Anabolic Response

scholarly journals Parathyroid hormone activates adhesion in bone marrow stromal precursor cells

2004 ◽  
Vol 180 (3) ◽  
pp. 505-513 ◽  
Author(s):  
J Davies ◽  
TJ Chambers
Keyword(s):  
Bone Marrow ◽  
Parathyroid Hormone ◽  
Interleukin 6 ◽  
Bone Marrow Cells ◽  
Early Event ◽  
Adherent Cells ◽  
Anabolic Response ◽  
Stromal Precursors ◽  
Marrow Cells

The ability of parathyroid hormone (PTH) to enhance bone formation has recently been exploited in the treatment of osteoporosis. However, the underlying mechanisms are unknown. Osteoblasts, the bone-forming cells, derive from multipotential bone marrow stromal precursors called colony-forming units-fibroblastic (CFU-F) upon culture ex vivo. Adhesion of such stromal precursors to bone is likely to be an early event in the anabolic response of bone to PTH. To test this, we measured the number of CFU-F that could be extracted from murine bone marrow after administration of an anabolic dose of PTH. We found that a very early response is a dramatic reduction, starting within 2 h, in the number of CFU-F that could be extracted from their bone marrow. We then tested whether PTH has the ability to activate adhesion of CFU-F in vitro. For this, bone marrow cells were incubated in PTH for varying times. Non-adherent cells were then removed, and the adherent cells were incubated in PTH-free medium for 14 days to assess, as colony formation, the number of CFU-F that had adhered in the preceding period. We found that incubation in PTH caused a substantial increase in the number of CFU-F that adhered within 24 h. This increase was abrogated by peptidic inhibitors of integrins. The increase did not seem to be mediated through a PTH-induced increase in interleukin-6, since interleukin-6 had no effect on CFU-F numbers when substituted for PTH. Similarly, adhesion was unaffected by incubation of bone marrow cells in dibutyryl cyclic AMP, nor by inhibitors or donors of nitric oxide. However, activation of CFU-F in vitro by PTH was strongly inhibited by indomethacin and mimicked by prostaglandin E(2), and indomethacin reversed the PTH-mediated reduction of CFU-F that could be extracted from mouse bone marrow. These results suggested that PTH rapidly activates adhesion of CFU-F to plastic or bone surfaces. This activation may represent an early event in the anabolic response of bone cells to PTH.

scholarly journals TG-interacting factor 1 (Tgif1)-deficiency attenuates bone remodeling and blunts the anabolic response to parathyroid hormone

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiroaki Saito ◽  
Andreas Gasser ◽  
Simona Bolamperti ◽  
Miki Maeda ◽  
Levi Matthies ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Remodeling ◽  
Anabolic Response
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