Low‐Intensity Pulsed Ultrasound Accelerates Traumatic Vertebral Fracture Healing by Coupling Proliferation of Type H Microvessels

Wu, Sui-Yi; Xu, Ximing; Sun, Jingchuan; Zhang, Yao; Shi, Jiangang; Xu, Tianming

doi:10.1002/jum.14525

Cited by 11 publications

(7 citation statements)

References 28 publications

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“…Also, low-intensity pulsed ultrasound treatment, which exhibits therapeutic potential for some skeletal diseases through increasing blood flow and angiogenesis, could accelerate traumatic vertebral fracture healing, with significantly higher density of type H vessels, coupled with increased osteogenesis and chondrogenesis. 82,83 Osteoarthritis Osteoarthritis is a progressive degenerative joint disease with the pathological features of articular cartilage degeneration, osteophyte formation, and subchondral bone edema and sclerosis. 84 The abundance and proliferation ability of type H vessels in subchondral bone, particularly in the so-called osteoid islets, were found to be markedly increased in anterior cruciate ligament transection rodent models.…”

Section: Osteoporosismentioning

confidence: 99%

Unique bone marrow blood vessels couple angiogenesis and osteogenesis in bone homeostasis and diseases

Zhao

Xie

2020

Annals of the New York Academy of Sciences

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Blood vessels serve as a versatile transport system and play crucial roles in organ development, regeneration, and stem cell behavior. In the skeletal system, certain capillaries support perivascular stem cells or osteoprogenitor cells and thereby regulate bone formation. Recent studies reported that a specialized capillary subtype, termed type H vessels, is shown to couple angiogenesis and osteogenesis in rodents and humans. They can be distinguished by specific cell surface markers, as the endothelial cells in the metaphysis and endosteum highly express the junctional protein CD31 and the sialoglycoprotein endomucin. Here, we provide an overview of the role of type H vessels in bone homeostasis and summarize their linkage with various cytokines to control bone cell behavior and bone formation. We also discuss the potential clinical application for bone disorders by targeting these specific vessels according to their physiological and pathobiological settings.

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Section: Osteoporosismentioning

confidence: 99%

Unique bone marrow blood vessels couple angiogenesis and osteogenesis in bone homeostasis and diseases

Zhao

Xie

2020

Annals of the New York Academy of Sciences

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“…S3A . That may be the possible reason for that the ultrasound stimulation could promote the healing of wounds or defects reported before [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, it is also discovered that in addition to diagnosis, ultrasound can be effectively applied for disease treatment according to its category. For example, high-intensity focused ultrasound (HIFUS) can be used for the ablation of malignant tissues [ 58 ], and low-intensity pulsed ultrasound (LIPUS) can be used for the adjuvant therapy of bone diseases [ 59 , 60 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis

Jing

Fan

Yao

et al. 2021

Regenerative Biomaterials

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Bone tissue with strong adaptability is often in a complex dynamical microenvironment in vivo, which is associated with the pathogenesis and treatment of orthopedic diseases. Therefore, it is of great significance to investigate the effects of corresponding compound stimulation on cell behaviors. Herein, a fluid shear stress (FSS) plus ultrasound stimulation platform suitable for cell studies based on a microfluidic chip was constructed and bone marrow mesenchymal stem cell (BMSC) was chosen as a model cell. The proliferation and osteogenesis of BMSCs under the compound stimulation of FSS plus ultrasound in growth medium without any soluble induction factors were firstly investigated. Single FSS stimulation and static culture conditions were also examined. Results illustrated that suitable single FSS stimulation (about 0.06 dyn/cm2) could significantly enhance cell proliferation and osteogenesis simultaneously when compared to the static control, while greater FSS mitigated or even restricted these enhancing effects. Interestingly, ultrasound stimulation combined with this suitable FSS stimulation further accelerated cell proliferation as the intensity of ultrasound increasing. As for the osteogenesis under compound stimulation, it was relatively restricted under lower ultrasound intensity (about 0.075 W/cm2), while promoted when the intensity became higher (about 1.75 W/cm2). This study suggests that both the cell proliferation and osteogenesis are very responsive to the magnitudes of FSS and ultrasound stimulations and can be both significantly enhanced by proper combination strategies. Moreover, these findings will provide valuable references for the construction of effective cell bioreactors and also the treatment of orthopedic diseases.

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“…Increased type‐H vessel abundance is reported to significantly accelerate bone fracture healing and spinal fusion in previous studies. [ 48 , 49 ] The close location relationship between type‐H vessel and CGRP positive nerves has been identified during the ossification of endplates in painful disc model. [ 11 ] This is also consistent with previous reports that CGRP has dual biological functions in terms of angiogenesis [ 18 ] and osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

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

Yao

et al. 2021

Advanced Science

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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 Ca 2+ /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.

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Low‐Intensity Pulsed Ultrasound Accelerates Traumatic Vertebral Fracture Healing by Coupling Proliferation of Type H Microvessels

Abstract: Low-intensity pulsed US could accelerate traumatic vertebral fracture healing by temporally and spatially increasing chondrogenesis and osteoblast-induced osteogenesis coupled with angiogenesis of type H microvessels in a rat model of traumatic vertebral fracture.

Cited by 11 publications

References 28 publications

Unique bone marrow blood vessels couple angiogenesis and osteogenesis in bone homeostasis and diseases

Unique bone marrow blood vessels couple angiogenesis and osteogenesis in bone homeostasis and diseases

Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis

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

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