title: PTH signaling mediates perilacunar remodeling during exercise.
abstract: Mechanical loading and release of endogenous parathyroid hormone (PTH) during exercise facilitate the adaptation of bone. However, it remains unclear how exercise and PTH influence the composition of bone and how exercise and PTH-mediated compositional changes influence the mechanical properties of bone. Thus, the primary purpose of this study was to establish compositional changes within osteocytes' perilacunar region of cortical bone following exercise, and evaluate the influence of endogenous PTH signaling on this perilacunar adaptation. Raman spectroscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS) were used to evaluate tissue composition surrounding individual lacuna within the tibia of 19week old male mice exposed to treadmill running for 3weeks. As a result of exercise, tissue within the perilacunar region (within 0-5μm of the lacuna wall) had a lower mineral-to-matrix ratio (MMR) compared to sedentary controls. In addition, exercise also increased the carbonate-to-phosphate ratio (CPR) across both perilacunar and non-perilacunar regions (5-10μm and 10-15μm from the lacuna walls). Tibial post-yield work had a significant negative correlation with perilacunar MMR. Inhibition of PTH activity with PTH(7-34) demonstrated that perilacunar remodeling during exercise was dependent on the cellular response to endogenous PTH. The osteocytes' response to endogenous PTH during exercise was characterized by a significant reduction in SOST expression and significant increase in FGF-23 expression. The potential reduction in phosphate levels due to FGF-23 expression may explain the increase in carbonate substitution. Overall, this is the first study to demonstrate that adaptation in tissue composition is localized around individual osteocytes, may contribute to the changes in whole bone mechanics during exercise, and that PTH signaling during exercise contributes to these adaptations.
authors.affiliation: Bone and Joint Center, Henry Ford Hospital, Detroit, MI 48202, USA; Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Gardinier
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Salam
authors.initials: S
authors.lastname: Al-Omaishi
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Morris
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: dhkohn@umich.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: Kohn
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D016723:Bone Remodeling; D005080:Exercise Test; D000089703:Fibroblast Growth Factor-23; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010281:Parathyroid Hormone / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000379:methods*; D015398:Signal Transduction; D013052:Spectrometry, X-Ray Emission; D013059:Spectrum Analysis, Raman; D013977:Tibia / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D000089703:Fibroblast Growth Factor-23
keywords: Exercise; Osteocyte; Parathyroid hormone; Perilacunar remodeling; Raman spectroscopy