Loss of the PTH/PTHrP receptor along the osteoblast lineage limits the anabolic response to exercise.

Joseph D Gardinier,Conor Daly-Seiler,Chunbin Zhang,Siddharth Kundal,Niloufar Rostami,Damian Christopher Genetos

doi:10.1371/journal.pone.0211076

Joseph D Gardinier, Conor Daly-Seiler + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0211076

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Journal: PloS one	Publication Date: Jan 25, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: Henry Ford Hospital, Wayne State University

Abstract

Exercise and physical activity are critical to maintain bone mass and strength throughout life. Both exercise and physical activity subject bone to a unique combination of stimuli in the forms of dynamic loading and a systemic increase in parathyroid hormone (PTH). Although dynamic loading is considered to be the primary osteogenic stimuli, the influence of increasing PTH levels remains unclear. We hypothesize that activation of the PTH/PTH-related peptide type 1 receptor (PPR) along the osteoblast lineage facilitates bone formation and improved mechanical properties in response to exercise. To test this hypothesis, conditional PPR-knockout mice (PPRcKO) were generated in which PPR expression was deleted along the osteoblast lineage under the osterix promoter. At 8-weeks of age, both PPRfl/fl and PPRcKO mice were subjected to treadmill running or sedentary conditions for 5-weeks. Under sedentary conditions, PPRcKO mice displayed significantly less bone mass as well as smaller structural-level strength (yield-load and ultimate load), while tissue level properties were largely unaffected. However, PPRcKO mice exposed to exercise displayed significantly less structural-level and tissue-level mechanical properties when compared to exercised PPRfl/fl mice. Overall, these data demonstrate that PPR expression along the osteoblast lineage is essential for exercise to improve the mechanical properties of cortical bone. Furthermore, the influence of PPR activation on material properties is unique to exercise and not during normal growth and development.

Highlights

The incidence and economic burden of osteoporotic fractures continues to grow each year.[1]
Genotype had a main effect on tibia length as well as cortical area and moment of inertia about the anterior-posterior axis (MOIA/P), each of which was significantly smaller in PPR-knockout mice (PPRcKO) mice compared to PPRfl/fl control mice (Table 1)
The present findings demonstrate that parathyroid hormone (PTH) signaling during exercise has a unique role in bone adaptation that is mediated through peptide type receptor (PPR) activation along the osteoblast lineage

Summary

Introduction

The incidence and economic burden of osteoporotic fractures continues to grow each year.[1] Maintaining bone mass and strength are critical to preventing osteoporosis and reducing fracture risk throughout life. Exercise and physical activity throughout life are key preventative measures recommended by the National Osteoporosis Foundation to reduce fracture risk.[2] Understanding the underlying mechanisms by which exercise regulates bone metabolism is essential to developing therapeutic strategies that reduce risk of osteoporosis and fracture.

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