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Regulation of bone remodeling by the central and peripheral nervous system
Open accessAbstract
The homeostatic nature of bone remodeling has become a notion further supported lately by the demonstration that neuropeptides and their receptors regulate osteoblast and osteoclast function in vivo. Following initial studies reporting the presence of nerves and nerve-derived products within the bone microenvironment and the expression of receptors for these neuropeptides in bone cells, new experimental and mechanistic evidence based on in vivo murine genetic and pharmacologic models recently demonstrated that inputs from the central and peripheral nervous system feed into the already complex regulatory machinery controlling bone remodeling. The function of a number of "osteo-neuromediators" has been characterized, including norepinephrine and the beta2-adrenergic receptor, Neuropeptide Y and the Y1 and Y2 receptors, endocannabinoids and the CB1 and CB2 receptors, as well as dopamine, serotonin and their receptors and transporters, Calcitonin gene-related peptide, and neuronal NOS. This new body of evidence suggests that neurons in the central nervous system integrate clues from the internal and external milieux, such as energy homeostasis, glycemia or reproductive signals, with the regulation of bone remodeling. The next major tasks in this new area of bone biology will be to understand, at the molecular level, the mechanisms by which common central neural systems regulate and integrate these major physiological functions, the relative importance of the central and peripheral actions of neuropeptides present in both compartments and their relationship, and how bone cells signal back to central centers, because the definition of a homeostatic function implies the existence of feedback signals. Together, these findings shed a new light on the complexity of the mechanisms regulating bone remodeling and uncovered new potential therapeutic strategies for the design of bone anabolic treatments. This review summarizes the latest advances in this area, focusing on investigations based on in vivo animal studies.
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“In these cavities, there is the formation of temporary anatomical structures called basic multicellular units (BMUs), which are comprised of a group of osteoclasts ahead forming the cutting cone and a group of osteoblasts behind forming the closing cone, associated with blood vessels and the peripheral innervation [11, 166].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [166]
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Metadata
- Authors
- Elefteriou, F.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Elefteriou, Florent
- ORCID
- Elefteriou, Florent
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 473
- Issue
- 2
- Pages
- 231-236
- ISSN
- 0003-9861 (ISSN-L)
- PMC
- PMC2430105
- OpenAlex
- W1963686806
- Cited by
- 229
- References
- 106
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 8 · 2021: 9 · 2020: 17 · 2019: 14 · 2018: 9 · 2017: 12 · 2016: 5 · 2015: 13 · 2014: 27 · 2013: 17 · 2012: 16
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058883, R21DK074994)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- bone remodeling, bone homeostasis, neuropeptides, norepinephrine, beta2-adrenergic receptor, neuropeptide Y, Y1 receptor, Y2 receptor, endocannabinoids, CB1 receptor, CB2 receptor, dopamine, serotonin, calcitonin gene-related peptide, neuronal nitric oxide synthase, osteoblasts, osteoclasts, central nervous system, peripheral nervous system, bone microenvironment, energy homeostasis, bone anabolic therapy
- MeSH terms
- Animals, Brain, Calcitonin, Humans, Hypothalamus, Neurons, Neuropeptide Y, Osteoblasts, Bone Remodeling, Receptors, Neuropeptide Y, Peripheral Nervous System
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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