The interdependent relationship between the nitric oxide signaling pathway and primary cilia in pulse electromagnetic field‐stimulated osteoblastic differentiation

He, Wen-Fang; Qin, Rong; Gao, Yubi; Zhou, Jian; Wei, Juan‐Juan; Liu, Jing; Hou, Xue‐Feng; Ma, Hui‐Ping; Chen, Xian; Li, Xueyan; Chen, Ke Ming

doi:10.1096/fj.202101577rr

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…We have previously reported that the existence of primary cilia is the precondition for the normal expression of BMP receptor‐II, soluble adenylyl cyclases, Wnt10b, or the ciliary components of the nitric oxide signaling pathway (He et al, 2022; Shi et al, 2017; Xie et al, 2016; Zhou et al, 2019). It was the first time that shortening/absorption of primary cilia was found to increase the expression level of TRPV4, which was located in primary cilia and expressed at a relative low level in normal condition.…”

Section: Discussionmentioning

confidence: 99%

Simulated microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

Miao,

Liu,

Sun

et al. 2023

Journal Cellular Physiology

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Oxidative stress has been considered to be closely related to spaceflight‐induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity‐induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca2+ overload, and the latter was found to be caused by increased activity of Ca2+ channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A‐elicited Ca2+ influx. Supplementation of HC‐067047, a specific antagonist of TRPV4, attenuated microgravity‐induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in primary cilia and expressed at low levels in NG, microgravity‐induced shortening of primary cilia led to increased TRPV4 levels and Ca2+ influx. When primary cilia were protected by miR‐129‐3p overexpression or supplementation with a natural flavonoid moslosooflavone, microgravity‐induced increased TRPV4 expression, mitochondrial dysfunction, oxidative stress, and osteogenesis loss were all prevented. Our data revealed a new mechanism that primary cilia function as a controller for TRPV4 expression. Microgravity‐induced injury on primary cilia leads to increased expression and overactive channel of TRPV4, causing intracellular Ca2+ overload and oxidative stress, and primary cilium protection could be an effective countermeasure against microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts.

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Section: Discussionmentioning

confidence: 99%

Simulated microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

Miao,

Liu,

Sun

et al. 2023

Journal Cellular Physiology

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“…Immobile cilia are also commonly referred to as primary cilia; they sense changes in the microenvironment surrounding the cell and mediate a variety of important signal transductions within the cell [ 34 , 35 , 36 ]. Wen-Fang He et al revealed that PEMFs promote osteogenic differentiation through nitric oxide signaling within primary cilia, thus inhibiting osteoporosis progression [ 37 ]. According to Yan-Fang Xie et al, PEMFs stimulated osteoblast differentiation and mineralization in a primary cilia-dependent manner and inhibited osteoporosis progression [ 38 ].…”

Section: Pemfs For Osteoporosismentioning

confidence: 99%

The Possible Role of Electrical Stimulation in Osteoporosis: A Narrative Review

Zhang

Luo

et al. 2023

Medicina

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Osteoporosis is mainly a geriatric disease with a high incidence, and the resulting spinal fractures and hip fractures cause great harm to patients. Anti-osteoporosis drugs are the main treatment for osteoporosis currently, but these drugs have potential clinical limitations and side effects, so the development of new therapies is of great significance to patients with osteoporosis. Electrical stimulation therapy mainly includes pulsed electromagnetic fields (PEMF), direct current (DC), and capacitive coupling (CC). Meanwhile, electrical stimulation therapy is clinically convenient without side effects. In recent years, many researchers have explored the use of electrical stimulation therapy for osteoporosis. Based on this, the role of electrical stimulation therapy in osteoporosis was summarized. In the future, electrical stimulation might become a new treatment for osteoporosis.

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“…It has been shown that primary cilia act as sensory organs involved in pulsed electromagnetic field-mediated bone formation ( 32 ). He ( 33 ) found that PEMF stimulates osteogenic differentiation mainly by activating the NOS/NO/sGC/cGMP/PKG signaling pathway and thus stimulating osteogenic differentiation, and it is noteworthy that all components of this signaling pathway, including iNOS, eNOS, sGC, PKG-1, and PKG-2 are localized in the primary cilia, and that eNOS needs to be phosphorylated within the primary cilia in order to be phosphorylated. As well as Liu ( 25 ) also reported that the primary cilia of osteoblasts in rats exposed to microgravity rapidly became shorter or even disappeared, and this phenomenon was accompanied by a significant reduction in osteogenic differentiation and mineralization of osteoblasts.…”

Section: The Role Of Primary Cilia In Bone Metabolismmentioning

confidence: 99%

Recent advances in primary cilia in bone metabolism

Lian,

Li,

et al. 2023

Front. Endocrinol.

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Primary cilia are microtubule-based organelles that are widespread on the cell surface and play a key role in tissue development and homeostasis by sensing and transducing various signaling pathways. The process of intraflagellar transport (IFT), which is propelled by kinesin and dynein motors, plays a crucial role in the formation and functionality of cilia. Abnormalities in the cilia or ciliary transport system often cause a range of clinical conditions collectively known as ciliopathies, which include polydactyly, short ribs, scoliosis, thoracic stenosis and many abnormalities in the bones and cartilage. In this review, we summarize recent findings on the role of primary cilia and ciliary transport systems in bone development, we describe the role of cilia in bone formation, cartilage development and bone resorption, and we summarize advances in the study of primary cilia in fracture healing. In addition, the recent discovery of crosstalk between integrins and primary cilia provides new insights into how primary cilia affect bone.

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The interdependent relationship between the nitric oxide signaling pathway and primary cilia in pulse electromagnetic field‐stimulated osteoblastic differentiation

Cited by 7 publications

References 41 publications

Simulated microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

Simulated microgravity‐induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

The Possible Role of Electrical Stimulation in Osteoporosis: A Narrative Review

Recent advances in primary cilia in bone metabolism

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