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The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

NMUR1 in the NMU-Mediated Regulation of Bone Remodeling

Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN 46022, USA
Bone and Muscle Research Group, Marian University, Indianapolis, IN 46022, USA
Department of Biology, The University of Scranton, Scranton, PA 18503, USA
Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Nicola Smania
Life 2021, 11(10), 1028;
Received: 23 August 2021 / Revised: 24 September 2021 / Accepted: 27 September 2021 / Published: 29 September 2021
(This article belongs to the Special Issue Metabolic Bone Diseases: From Classroom to Clinic)
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. View Full-Text
Keywords: Neuromedin-U; NMU; NMUR1; NMUR2; bone; osteoblast; osteoporosis Neuromedin-U; NMU; NMUR1; NMUR2; bone; osteoblast; osteoporosis
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MDPI and ACS Style

Hsiao, Y.-T.; Manikowski, K.J.; Snyder, S.; Griffin, N.; Orr, A.L.; Hulsey, E.Q.; Born-Evers, G.; Zukosky, T.; Squire, M.E.; Hum, J.M.; Metzger, C.E.; Allen, M.R.; Lowery, J.W. NMUR1 in the NMU-Mediated Regulation of Bone Remodeling. Life 2021, 11, 1028.

AMA Style

Hsiao Y-T, Manikowski KJ, Snyder S, Griffin N, Orr AL, Hulsey EQ, Born-Evers G, Zukosky T, Squire ME, Hum JM, Metzger CE, Allen MR, Lowery JW. NMUR1 in the NMU-Mediated Regulation of Bone Remodeling. Life. 2021; 11(10):1028.

Chicago/Turabian Style

Hsiao, Yu-Tin, Kelli J. Manikowski, Samantha Snyder, Nicole Griffin, Ashley L. Orr, Elizabeth Q. Hulsey, Gabriella Born-Evers, Tara Zukosky, Maria E. Squire, Julia M. Hum, Corinne E. Metzger, Matthew R. Allen, and Jonathan W. Lowery. 2021. "NMUR1 in the NMU-Mediated Regulation of Bone Remodeling" Life 11, no. 10: 1028.

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