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Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.
PLoS One. 2018; 13(2):e0192760.Plos

Abstract

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<0.05). However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the molecular events involved in regulation of bone adaptation is needed to understand the timing and impact of loading events, and the contribution of the neuronal signaling to functional adaptation of bone.

Authors+Show Affiliations

Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America. College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia. Australian Institute of Musculoskeletal Science (AIMSS), Victoria University, St Albans, Victoria, Australia.Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29486004

Citation

Bleedorn, Jason A., et al. "Temporal Mechanically-induced Signaling Events in Bone and Dorsal Root Ganglion Neurons After in Vivo Bone Loading." PloS One, vol. 13, no. 2, 2018, pp. e0192760.
Bleedorn JA, Hornberger TA, Goodman CA, et al. Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading. PLoS ONE. 2018;13(2):e0192760.
Bleedorn, J. A., Hornberger, T. A., Goodman, C. A., Hao, Z., Sample, S. J., Amene, E., Markel, M. D., Behan, M., & Muir, P. (2018). Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading. PloS One, 13(2), e0192760. https://doi.org/10.1371/journal.pone.0192760
Bleedorn JA, et al. Temporal Mechanically-induced Signaling Events in Bone and Dorsal Root Ganglion Neurons After in Vivo Bone Loading. PLoS ONE. 2018;13(2):e0192760. PubMed PMID: 29486004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading. AU - Bleedorn,Jason A, AU - Hornberger,Troy A, AU - Goodman,Craig A, AU - Hao,Zhengling, AU - Sample,Susannah J, AU - Amene,Ermias, AU - Markel,Mark D, AU - Behan,Mary, AU - Muir,Peter, Y1 - 2018/02/27/ PY - 2017/11/16/received PY - 2018/01/30/accepted PY - 2018/2/28/entrez PY - 2018/2/28/pubmed PY - 2018/4/13/medline SP - e0192760 EP - e0192760 JF - PloS one JO - PLoS ONE VL - 13 IS - 2 N2 - 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<0.05). However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the molecular events involved in regulation of bone adaptation is needed to understand the timing and impact of loading events, and the contribution of the neuronal signaling to functional adaptation of bone. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/29486004/Temporal_mechanically-induced_signaling_events_in_bone_and_dorsal_root_ganglion_neurons_after_in_vivo_bone_loading L2 - http://dx.plos.org/10.1371/journal.pone.0192760 DB - PRIME DP - Unbound Medicine ER -