ArticleThe Journal of biological chemistry2013
Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 64 citations in OpenAlex.
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- The therapeutic potential of descending regulatory pathways from brain to bone in osteoporosis: focusing on the brain-bone axis.Frontiers in endocrinology · 2026Review
- Methylphenidate-effects on orthodontic tooth movement, orthodontically induced and nonorthodontic root resorption? : A micro-computed tomography and immunohistochemical analysis.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2026Article
- Brain-Bone Axis in Physiological and Pathological Conditions.International journal of molecular sciences · 2025Review
- Autonomic Nervous System in Bone Remodeling: From Mechanisms to Novel Therapies in Orthopedic Diseases.Orthopaedic surgery · 2025Review
- The autonomic nervous system and bone health in chronic kidney disease.European journal of clinical investigation · 2025Review
- Palmitoylation regulates norepinephrine transporter uptake, surface localization, and total expression with pathogenic implications in postural orthostatic tachycardia syndrome.Journal of neurochemistry · 2025Article
- Skeletal interoception and prospective application in biomaterials for bone regeneration.Bone research · 2025Review
- The influence of adrenoceptor blocker treatment on fracture healing in osteoporotic and non-osteoporotic bone.Frontiers in physiology · 2025Article
- Unraveling the Bone-Brain Axis: A New Frontier in Parkinson's Disease Research.International journal of molecular sciences · 2024Review
- Using tissue clearing and light sheet fluorescence microscopy for the three-dimensional analysis of sensory and sympathetic nerve endings that innervate bone and dental tissue of mice.The Journal of comparative neurology · 2024Article
- Effects of fish oil supplementation on bone turnover markers in depression: a pilot study.Frontiers in nutrition · 2024Article
- The selective norepinephrine reuptake inhibitor reboxetine promotes late-stage fracture healing in mice.iScience · 2023Article
- Interoceptive regulation of skeletal tissue homeostasis and repair.Bone research · 2023Review
- Beta 2 Adrenergic Receptor Selective Antagonist Enhances Mechanically Stimulated Bone Anabolism in Aged Mice.JBMR plus · 2023Article
- The Role of Sympathetic Nerves in Osteoporosis: A Narrative Review.Biomedicines · 2022Review
- Mental health and periodontal and peri-implant diseases.Periodontology 2000 · 2022Review
- Psychostimulants Modafinil, Atomoxetine and Guanfacine Impair Bone Cell Differentiation and MSC Migration.International journal of molecular sciences · 2022Article
- Myeloid cell-derived catecholamines influence bone turnover and regeneration in mice.Frontiers in endocrinology · 2022Article
- Response of the periodontal tissues to β-adrenergic stimulation.Life sciences · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Changes in bone remodeling induced by pharmacological and genetic manipulation of β-adrenergic receptor (βAR) signaling in osteoblasts support a role of sympathetic nerves in the regulation of bone remodeling. However, the contribution of endogenous sympathetic outflow and nerve-derived norepinephrine (NE) to bone remodeling under pathophysiological conditions remains unclear. We show here that differentiated osteoblasts, like neurons, express the norepinephrine transporter (NET), exhibit specific NE uptake activity via NET and can catabolize, but not generate, NE. Pharmacological blockade of NE transport by reboxetine induced bone loss in WT mice. Similarly, lack of NE reuptake in norepinephrine transporter (Net)-deficient mice led to reduced bone formation and increased bone resorption, resulting in suboptimal peak bone mass and mechanical properties associated with low sympathetic outflow and high plasma NE levels. Last, daily sympathetic activation induced by mild chronic stress was unable to induce bone loss, unless NET activity was blocked. These findings indicate that the control of endogenous NE release and reuptake by presynaptic neurons and osteoblasts is an important component of the complex homeostatic machinery by which the sympathetic nervous system controls bone remodeling. These findings also suggest that drugs antagonizing NET activity, used for the treatment of hyperactivity disorders, may have deleterious effects on bone accrual.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.