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NMUR1 in the NMU-Mediated Regulation of Bone Remodeling

Neuromedin-U (NMU) is an evolutionarily conserved peptide that regulates varying physiologic effects including blood pressure, stress and allergic responses, metabolic and feeding behavior, pain perception, and neuroendocrine functions. Recently, several lines of investigation implicate NMU in regul...

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Autores principales: Hsiao, Yu-Tin, Manikowski, Kelli J., Snyder, Samantha, Griffin, Nicole, Orr, Ashley L., Hulsey, Elizabeth Q., Born-Evers, Gabriella, Zukosky, Tara, Squire, Maria E., Hum, Julia M., Metzger, Corinne E., Allen, Matthew R., Lowery, Jonathan W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538501/
https://www.ncbi.nlm.nih.gov/pubmed/34685399
http://dx.doi.org/10.3390/life11101028
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author Hsiao, Yu-Tin
Manikowski, Kelli J.
Snyder, Samantha
Griffin, Nicole
Orr, Ashley L.
Hulsey, Elizabeth Q.
Born-Evers, Gabriella
Zukosky, Tara
Squire, Maria E.
Hum, Julia M.
Metzger, Corinne E.
Allen, Matthew R.
Lowery, Jonathan W.
author_facet Hsiao, Yu-Tin
Manikowski, Kelli J.
Snyder, Samantha
Griffin, Nicole
Orr, Ashley L.
Hulsey, Elizabeth Q.
Born-Evers, Gabriella
Zukosky, Tara
Squire, Maria E.
Hum, Julia M.
Metzger, Corinne E.
Allen, Matthew R.
Lowery, Jonathan W.
author_sort Hsiao, Yu-Tin
collection PubMed
description Neuromedin-U (NMU) is an evolutionarily conserved peptide that regulates varying physiologic effects including blood pressure, stress and allergic responses, metabolic and feeding behavior, pain perception, and neuroendocrine functions. Recently, several lines of investigation implicate NMU in regulating bone remodeling. For instance, global loss of NMU expression in male and female mice leads to high bone mass due to elevated bone formation rate with no alteration in bone resorption rate or observable defect in skeletal patterning. Additionally, NMU treatment regulates the activity of osteoblasts in vitro. The downstream pathway utilized by NMU to carry out these effects is unknown as NMU signals via two G-protein-coupled receptors (GPCRs), NMU receptor 1 (NMUR1), and NMU receptor 2 (NMUR2), and both are expressed in the postnatal skeleton. Here, we sought to address this open question and build a better understanding of the downstream pathway utilized by NMU. Our approach involved the knockdown of Nmur1 in MC3T3-E1 cells in vitro and a global knockout of Nmur1 in vivo. We detail specific cell signaling events (e.g., mTOR phosphorylation) that are deficient in the absence of NMUR1 expression yet trabecular bone volume in femora and tibiae of 12-week-old male Nmur1 knockout mice are unchanged, compared to controls. These results suggest that NMUR1 is required for NMU-dependent signaling in MC3T3-E1 cells, but it is not required for the NMU-mediated effects on bone remodeling in vivo. Future studies examining the role of NMUR2 are required to determine the downstream pathway utilized by NMU to regulate bone remodeling in vivo.
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spelling pubmed-85385012021-10-24 NMUR1 in the NMU-Mediated Regulation of Bone Remodeling Hsiao, Yu-Tin Manikowski, Kelli J. Snyder, Samantha Griffin, Nicole Orr, Ashley L. Hulsey, Elizabeth Q. Born-Evers, Gabriella Zukosky, Tara Squire, Maria E. Hum, Julia M. Metzger, Corinne E. Allen, Matthew R. Lowery, Jonathan W. Life (Basel) Article Neuromedin-U (NMU) is an evolutionarily conserved peptide that regulates varying physiologic effects including blood pressure, stress and allergic responses, metabolic and feeding behavior, pain perception, and neuroendocrine functions. Recently, several lines of investigation implicate NMU in regulating bone remodeling. For instance, global loss of NMU expression in male and female mice leads to high bone mass due to elevated bone formation rate with no alteration in bone resorption rate or observable defect in skeletal patterning. Additionally, NMU treatment regulates the activity of osteoblasts in vitro. The downstream pathway utilized by NMU to carry out these effects is unknown as NMU signals via two G-protein-coupled receptors (GPCRs), NMU receptor 1 (NMUR1), and NMU receptor 2 (NMUR2), and both are expressed in the postnatal skeleton. Here, we sought to address this open question and build a better understanding of the downstream pathway utilized by NMU. Our approach involved the knockdown of Nmur1 in MC3T3-E1 cells in vitro and a global knockout of Nmur1 in vivo. We detail specific cell signaling events (e.g., mTOR phosphorylation) that are deficient in the absence of NMUR1 expression yet trabecular bone volume in femora and tibiae of 12-week-old male Nmur1 knockout mice are unchanged, compared to controls. These results suggest that NMUR1 is required for NMU-dependent signaling in MC3T3-E1 cells, but it is not required for the NMU-mediated effects on bone remodeling in vivo. Future studies examining the role of NMUR2 are required to determine the downstream pathway utilized by NMU to regulate bone remodeling in vivo. MDPI 2021-09-29 /pmc/articles/PMC8538501/ /pubmed/34685399 http://dx.doi.org/10.3390/life11101028 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsiao, Yu-Tin
Manikowski, Kelli J.
Snyder, Samantha
Griffin, Nicole
Orr, Ashley L.
Hulsey, Elizabeth Q.
Born-Evers, Gabriella
Zukosky, Tara
Squire, Maria E.
Hum, Julia M.
Metzger, Corinne E.
Allen, Matthew R.
Lowery, Jonathan W.
NMUR1 in the NMU-Mediated Regulation of Bone Remodeling
title NMUR1 in the NMU-Mediated Regulation of Bone Remodeling
title_full NMUR1 in the NMU-Mediated Regulation of Bone Remodeling
title_fullStr NMUR1 in the NMU-Mediated Regulation of Bone Remodeling
title_full_unstemmed NMUR1 in the NMU-Mediated Regulation of Bone Remodeling
title_short NMUR1 in the NMU-Mediated Regulation of Bone Remodeling
title_sort nmur1 in the nmu-mediated regulation of bone remodeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538501/
https://www.ncbi.nlm.nih.gov/pubmed/34685399
http://dx.doi.org/10.3390/life11101028
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