Pain-sensing neurons mobilize blood stem cells from bone marrow

Tikhonova, Anastasia; Aifantis, Iannis

doi:10.1038/d41586-020-03577-7

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…A novel direct mechanism by which sensory nerves regulates HSC mobilization in bone marrow was also found recently 9,15 . Sensory nerves are critical in osteoclastogenesis, since patients with hereditary sensory neuropathy were reported to have no osteoclasts in the areas of severely degenerated sensory nerves 16 .…”

Section: Introductionsupporting

confidence: 54%

Sensory nerves directly promote osteoclastogenesis by secreting Cyp40

Pei¹,

Yang²,

Li³

et al. 2021

Preprint

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BackgroundGiven the afferent functions, sensors have been found exerting efferent influences and directly alter organ physiology. Sensory nerves have been found critical in osteoclasts and bone resorption. However, the direct evidence of whether sensory nerve efferent influences osteoclast, remains lacking. MethodsWe treated mice with resiniferatoxin (RTX) or complete Freund’s adjuvant (CFA) to induce sensory hypersensitivity. Bone histomorphometry including micro-ct, three-point bending assay, von kossa staining, calcein double labeling, toluidine blue staining, and trap staining were performed to monitor bone quality and bone cells. Multiple virus vectors were applied to trace signals between sensory nerves and osteoclasts. Sensory neurons (SN) and osteoclasts were cocultured to study the effects and mechanisms of the sensory nerves on osteoclasts in vitro. Isobaric tag for relative and absolute quantitation (iTRAQ) was used to identify secreted proteins in the sensory nerve. ResultsHere, we found sensory hypersensitivity significantly increased osteoclast bone resorption; SN directly promote osteoclastogenesis in vitro; and abundant sensory efferent signals transported into osteoclasts. Then our screening identified a novel neuropeptide Peptidyl-prolyl cis-trans isomerase D (Cyp40), is the reverse signal from the sensory nerve and plays a critical role for osteoclastogenesis, via aryl hydrocarbon receptor (AhR)-Ras/Raf-pErk-NFATc1 pathway. The efferent signals from sensory nerves tend to involves in the rapid feedback process: vast majority of sensory efferent signals (87.28%) present in fast-twitch myofibers. ConclusionThis study revealed a novel mechanism of sensory nerves on osteoclasts: the direct promotion of osteoclastogenesis by the Cyp40. This mechanism may represent a direct, and quick response of sensory nerves to the changes in bone. Targeting the Cyp40 could therefore be a strategy to promote bone repair at the early stage of bone injury.

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Section: Introductionsupporting

confidence: 54%

Sensory nerves directly promote osteoclastogenesis by secreting Cyp40

Pei¹,

Yang²,

Li³

et al. 2021

Preprint

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“…The administration of CGRP combined with G-CSF greatly improved HSC mobilization. CGRP binds directly to HSCs through a receptor dimer comprising the calcitonin receptor-like receptor (CALCRL) and receptor activity modifying protein 1 (RAMP1) and then mobilizes HSCs by activating downstream Gα s –adenylyl cyclase–cAMP signaling [ 79 80 ] [ Figure 3 ]. Notably, feeding mice with capsaicin can stimulate the nociceptors to release CGRP and mobilize HSCs [ 79 80 ] [ Figure 3 ].…”

Section: P Ain-sensing Nerve Cells (Nociceptors) Control He...mentioning

confidence: 99%

Hematopoietic stem cell mobilization

Sun

Chang

Liou

2022

Tzu Chi Medical Journal

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A BSTRACT Hematopoietic stem cell (HSC) transplantation has been used to treat hematopoietic diseases for over 50 years. HSCs can be isolated from bone marrow (BM), umbilical cord blood, or peripheral blood. Because of lower costs, shorter hospitalization, and faster engraftment, peripheral blood has become the predominant source of HSCs for transplantation. The major factors determining the rate of successful HSC transplantation include the degree of human leukocyte antigen matching between the donor and recipient and the number of HSCs for transplantation. Administration of granulocyte colony-stimulating factor (G-CSF) alone or combined with plerixafor (AMD3100) are clinical used methods to promote HSC mobilization from BM to the peripheral blood for HSC transplantations. However, a significant portion of healthy donors or patients may be poor mobilizers of G-CSF, resulting in an insufficient number of HSCs for the transplantation and necessitating alternative strategies to increase the apheresis yield. The detailed mechanisms underlying G-CSF-mediated HSC mobilization remain to be elucidated. This review summarizes the current research on deciphering the mechanism of HSC mobilization.

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“…Multiple studies have demonstrated the direct effect of sensory nerves on osteoblasts and bone formation 15,16,17 . Recently, a novel direct mechanism was identified by which sensory nerves regulate HSC mobilization in the bone marrow 18,19 .…”

Section: Introductionmentioning

confidence: 99%

Sensory nerves directly promote osteoclastogenesis by secreting Peptidyl-prolyl cis-trans isomerase D (Cyp40)

Pei

Yang

Liu

et al. 2023

Preprint

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Given the afferent functions, sensory nerves recently have been found exerting efferent influences and directly alter organ physiology. Moreover, studies have demonstrated the crucial role of sensory nerves in the physiological function of osteoclasts. However, the direct evidence of whether sensory nerve efferent influences osteoclast, remains lacking. Here, we found abundant efferent signals transported from sensory nerves into osteoclasts; sensory hypersensitivity significantly increased osteoclastic bone resorption; and sensory neurons (SN) directly promote osteoclastogenesis in vitro co-culture system. Then our screening identified a novel neuropeptide Cyp40, is the efferent signal from the sensory nerve and plays a critical role in the osteoclastogenesis, via aryl hydrocarbon receptor (AhR)-Ras/Raf-pErk-NFATc1 pathway. These findings revealed a novel mechanism of sensory nerves on bone regulation: the direct promotion of osteoclastogenesis by secreting Cyp40. Inhibiting the Cyp40 could therefore be a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.

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Pain-sensing neurons mobilize blood stem cells from bone marrow

Cited by 5 publications

References 10 publications

Sensory nerves directly promote osteoclastogenesis by secreting Cyp40

Sensory nerves directly promote osteoclastogenesis by secreting Cyp40

Hematopoietic stem cell mobilization

Sensory nerves directly promote osteoclastogenesis by secreting Peptidyl-prolyl cis-trans isomerase D (Cyp40)

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