Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide

Jie Mi; Jian Kun Xu; Zhi Yao; Hao Yao; Ye Li; Xuan He; Bing Yang Dai; Li Zou; Wen Xue Tong; Xiaotian Zhang; Peijie Hu; Yechun Ruan; Ning Tang; Xia Guo; Jie Zhao; Ju Fang He; Ling Qin

doi:10.1002/advs.202103005

Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide

Jie Mi, Jian Kun Xu, Zhi Yao, Hao Yao, Ye Li, Xuan He, Bing Yang Dai, Li Zou, Wen Xue Tong, Xiaotian Zhang, Peijie Hu, Yechun Ruan, Ning Tang, Xia Guo, Jie Zhao, Ju Fang He, Ling Qin

Research output: Journal article publication › Journal article › Academic research › peer-review

60 Citations (Scopus)

Abstract

The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene-related peptide (CGRP) by activating Ca²⁺/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type-H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES-enhanced osteoporotic fracture healing. This proof-of-concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.

Original language	English
Journal	Advanced Science
DOIs	https://doi.org/10.1002/advs.202103005
Publication status	Published - 28 Oct 2021

Keywords

bone regeneration
CGRP
dorsal root ganglions
electrical stimulation

ASJC Scopus subject areas

Medicine (miscellaneous)
General Chemical Engineering
General Materials Science
Biochemistry, Genetics and Molecular Biology (miscellaneous)
General Engineering
General Physics and Astronomy

More information

10.1002/advs.202103005

Cite this

@article{eeeb24cceac549dcb30c8e3b259319c9,

title = "Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide",

abstract = "The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene-related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type-H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES-enhanced osteoporotic fracture healing. This proof-of-concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.",

keywords = "bone regeneration, CGRP, dorsal root ganglions, electrical stimulation",

author = "Jie Mi and Xu, {Jian Kun} and Zhi Yao and Hao Yao and Ye Li and Xuan He and Dai, {Bing Yang} and Li Zou and Tong, {Wen Xue} and Xiaotian Zhang and Peijie Hu and Yechun Ruan and Ning Tang and Xia Guo and Jie Zhao and He, {Ju Fang} and Ling Qin",

note = "Funding Information: J.M., J.K.X., and Z.Y. contributed equally to this work. This project was supported by Hong Kong Research Grant Council (RGC) General Research Fund (Ref. No. 14117319), RGC Areas of Excellence (Ref. No. AoE/M‐402/20), RGC Theme‐based Research Scheme (Ref. No. T13‐402/17‐N), RGC Collaborative Research Fund (Ref. No. C4026‐17WF), and the National Natural Science Foundation of China (Ref. No. 81802152). Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH",

year = "2021",

month = oct,

day = "28",

doi = "10.1002/advs.202103005",

language = "English",

journal = "Advanced Science",

issn = "2198-3844",

publisher = "Wiley-VCH Verlag",

}

TY - JOUR

T1 - Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide

AU - Mi, Jie

AU - Xu, Jian Kun

AU - Yao, Zhi

AU - Yao, Hao

AU - Li, Ye

AU - He, Xuan

AU - Dai, Bing Yang

AU - Zou, Li

AU - Tong, Wen Xue

AU - Zhang, Xiaotian

AU - Hu, Peijie

AU - Ruan, Yechun

AU - Tang, Ning

AU - Guo, Xia

AU - Zhao, Jie

AU - He, Ju Fang

AU - Qin, Ling

N1 - Funding Information: J.M., J.K.X., and Z.Y. contributed equally to this work. This project was supported by Hong Kong Research Grant Council (RGC) General Research Fund (Ref. No. 14117319), RGC Areas of Excellence (Ref. No. AoE/M‐402/20), RGC Theme‐based Research Scheme (Ref. No. T13‐402/17‐N), RGC Collaborative Research Fund (Ref. No. C4026‐17WF), and the National Natural Science Foundation of China (Ref. No. 81802152). Publisher Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

PY - 2021/10/28

Y1 - 2021/10/28

N2 - The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene-related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type-H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES-enhanced osteoporotic fracture healing. This proof-of-concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.

AB - The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene-related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type-H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES-enhanced osteoporotic fracture healing. This proof-of-concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.

KW - bone regeneration

KW - CGRP

KW - dorsal root ganglions

KW - electrical stimulation

UR - http://www.scopus.com/inward/record.url?scp=85117909532&partnerID=8YFLogxK

U2 - 10.1002/advs.202103005

DO - 10.1002/advs.202103005

M3 - Journal article

AN - SCOPUS:85117909532

SN - 2198-3844

JO - Advanced Science

JF - Advanced Science

ER -

Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide

Abstract

Keywords

ASJC Scopus subject areas

More information

Other files and links

Fingerprint

Cite this