Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading

Autor:	Zhengling Hao, Ermias Amene, Peter Muir, Jason A. Bleedorn, Mark D. Markel, Craig A. Goodman, Mary Behan, Troy A. Hornberger, Susannah J. Sample
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	Male 0301 basic medicine MAPK/ERK pathway Cell signaling Organogenesis Gene Expression Ulna Signal transduction ERK signaling cascade Rats Sprague-Dawley Phosphatidylinositol 3-Kinases Dorsal root ganglion Animal Cells Neurotrophic factors Ganglia Spinal Medicine and Health Sciences Biomechanics Phosphorylation Connective Tissue Cells Neurons Multidisciplinary Protein Kinase Signaling Cascade Chemistry TOR Serine-Threonine Kinases Bone and Joint Mechanics Signaling cascades Cell biology medicine.anatomical_structure Connective Tissue Osteocyte Medicine Cellular Types Anatomy Research Article MAPK signaling cascades MAP Kinase Signaling System Science Osteocytes Bone and Bones 03 medical and health sciences Genetics medicine Animals Protein kinase B PI3K/AKT/mTOR pathway Osteoblasts Bone Development Biology and life sciences Rats Biological Tissue 030104 developmental biology Nerve growth factor Cellular Neuroscience Stress Mechanical Organism Development Neuroscience Developmental Biology
Zdroj:	PLoS ONE, Vol 13, Iss 2, p e0192760 (2018) PLoS ONE
ISSN:	1932-6203
Popis:	Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR). However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK’s, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), c-jun, and c-fos in dorsal root ganglion (DRG) of the brachial intumescence were performed. There was a significant increase in signaling through MAPK’s including extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P
Databáze:	OpenAIRE
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