Effects of β-adrenergic Stimulation on Bone-marrow Function in Normal and Sublethally Irradiated Mice

Lipski, S

doi:10.1080/09553007614550411

Cited by 13 publications

(5 citation statements)

References 13 publications

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“…Our data do not clearly demonstrate whether the effects of norepinephrine on HSPCs following radiation are direct or indirect. We observed that HSPCs expressed β-adrenergic receptors, in agreement with other studies of mice and human HSPCs [ 62 – 64 ]. However, the data indicating that treatment with a β-adrenergic agonist was insufficient to protect cells in vitro suggests a model in which cold-stress mediated β-adrenergic signaling suppresses apoptosis through indirect mechanisms.…”

Section: Discussionsupporting

confidence: 92%

Standard Sub-Thermoneutral Caging Temperature Influences Radiosensitivity of Hematopoietic Stem and Progenitor Cells

et al. 2015

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The production of new blood cells relies on a hierarchical network of hematopoietic stem and progenitor cells (HSPCs). To maintain lifelong hematopoiesis, HSPCs must be protected from ionizing radiation or other cytotoxic agents. For many years, murine models have been a valuable source of information regarding factors that either enhance or reduce the survival of HSPCs after exposure of marrow to ionizing radiation. In a recent series of studies, however, it has become clear that housing-related factors such as the cool room temperature required for laboratory mice can exert a surprising influence on the outcome of experiments. Here we report that the mild, but chronic cold-stress endured by mice housed under these conditions exerts a protective effect on HSPCs after both non-lethal and lethal doses of total body irradiation (TBI). Alleviation of this cold-stress by housing mice at a thermoneutral temperature (30°C) resulted in significantly greater baseline radiosensitivity to a lethal dose of TBI with more HSPCs from mice housed at thermoneutral temperature undergoing apoptosis following non-lethal TBI. Cold-stressed mice have elevated levels of norepinephrine, a key molecule of the sympathetic nervous system that binds to β-adrenergic receptors. We show that blocking this signaling pathway in vivo through use of the β-blocker propanolol completely mitigates the protective effect of cold-stress on HSPC apoptosis. Collectively this study demonstrates that chronic stress endured by the standard housing conditions of laboratory mice increases the resistance of HSPCs to TBI-induced apoptosis through a mechanism that depends upon β-adrenergic signaling. Since β-blockers are commonly prescribed to a wide variety of patients, this information could be important when predicting the clinical impact of HSPC sensitivity to TBI.

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Section: Discussionsupporting

confidence: 92%

Standard Sub-Thermoneutral Caging Temperature Influences Radiosensitivity of Hematopoietic Stem and Progenitor Cells

et al. 2015

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“…The in vivo biological relevance of postsynaptic ␤AR signaling has been addressed pharmacologically and genetically. Daily ␤AR stimulation by means of the ␤1/␤2AR nonselective agonist ISO or by ␤2AR-selective pharmacological agonists triggers a bone catabolic response measured by increased osteoclast formation, reduced osteoblast func- tion, and bone loss (39,56,181,278,301). The opposite manipulation, i.e., ␤AR blockade by the nonselective ␤1/ ␤2AR antagonist propranolol, is anti-catabolic, and this action on the skeleton is best seen in conditions where bone remodeling is high.…”

Section: B ␤Ars As Effector Of Sns Action In Bone Cellsmentioning

confidence: 99%

Impact of the Autonomic Nervous System on the Skeleton

Elefteriou

2018

Physiological Reviews

146

170

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It is from the discovery of leptin and the central nervous system as a regulator of bone remodeling that the presence of autonomic nerves within the skeleton transitioned from a mere histological observation to the mechanism whereby neurons of the central nervous system communicate with cells of the bone microenvironment and regulate bone homeostasis. This shift in paradigm sparked new preclinical and clinical investigations aimed at defining the contribution of sympathetic, parasympathetic, and sensory nerves to the process of bone development, bone mass accrual, bone remodeling, and cancer metastasis. The aim of this article is to review the data that led to the current understanding of the interactions between the autonomic and skeletal systems and to present a critical appraisal of the literature, bringing forth a schema that can put into physiological and clinical context the main genetic and pharmacological observations pointing to the existence of an autonomic control of skeletal homeostasis. The different types of nerves found in the skeleton, their functional interactions with bone cells, their impact on bone development, bone mass accrual and remodeling, and the possible clinical or pathophysiological relevance of these findings are discussed.

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“…There are three βAR: β1-, β2-, and β3ARs. Effects of adrenal extracts (containing the catecholamines NE and epinephrine) on bone growth were first noted in the 1950s [31], followed by observations of increased cyclic AMP (cAMP) upon epinephrine or isoproterenol treatment of bone marrow cells in the 1970s [32–35]. However, it took another decade for researchers to propose the functional relevance of βAR stimulation specifically in osteoblastic cells, when comparing PTH and calcitonin-induced increases in cAMP during in vitro studies using UMR 106 rat osteosarcoma cells [36].…”

Section: βAr Signaling In Osteoblastsmentioning

confidence: 99%

Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

2013

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The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis.

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Effects of β-adrenergic Stimulation on Bone-marrow Function in Normal and Sublethally Irradiated Mice

Cited by 13 publications

References 13 publications

Standard Sub-Thermoneutral Caging Temperature Influences Radiosensitivity of Hematopoietic Stem and Progenitor Cells

Standard Sub-Thermoneutral Caging Temperature Influences Radiosensitivity of Hematopoietic Stem and Progenitor Cells

Impact of the Autonomic Nervous System on the Skeleton

Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

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