A critical role of the K<sub>Ca</sub>3.1 channel in mechanical stretch‐induced proliferation of rat bone marrow‐derived mesenchymal stem cells

Jia, Xiaoling; Su, Hao; Chen, Xinlan; Huang, Yangbi; Zheng, Yufan; Pei, Jian; Gao, Chao; Gong, Xianghui; Huang, Yan; Jiang, Lin‐Hua; Fan, Yubo

doi:10.1111/jcmm.15014

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…We and other groups have shown that the expression and activity of the IK Ca channel in VSMCs and other cell types such as endothelial cells and MSCs are sensitive to regulation by mechanical forces, such as shear stress or membrane stretch (Brakemeier et al, 2003; Hayabuchi et al, 2011; Jia et al, 2020; Takai et al, 2013). It is interesting to examine whether vascular stiffening‐related mechanical stimulation regulates the IK Ca channel expression and activity in VSMCs and thereby VSMC proliferation.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IK_Ca channel‐dependent Ca²⁺ signaling

Jia

Yang

Gao

et al. 2021

Journal Cellular Physiology

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Vascular stiffening, an early and common characteristic of cardiovascular diseases (CVDs), stimulates vascular smooth muscle cell (VSMC) proliferation which reciprocally accelerates the progression of CVDs. However, the mechanisms by which extracellular matrix stiffness accompanying vascular stiffening regulates VSMC proliferation remain largely unknown. In the present study, we examined the role of the intermediate‐conductance Ca2+‐activated K+ (IKCa) channel in the matrix stiffness regulation of VSMC proliferation by growing A7r5 cells on soft and stiff polydimethylsiloxane substrates with stiffness close to these of arteries under physiological and pathological conditions, respectively. Stiff substrates stimulated cell proliferation and upregulated the expression of the IKCa channel. Stiff substrate‐induced cell proliferation was suppressed by pharmacological inhibition using TRAM34, an IKCa channel blocker, or genetic depletion of the IKCa channel. In addition, stiff substrate‐induced cell proliferation was also suppressed by reducing extracellular Ca2+ concentration using EGTA or intracellular Ca2+ concentration using BAPTA‐AM. Moreover, stiff substrate induced activation of extracellular signal‐regulated kinases (ERKs), which was inhibited by treatment with TRAM34 or BAPTA‐AM. Stiff substrate‐induced cell proliferation was suppressed by treatment with PD98059, an ERK inhibitor. Taken together, these results show that substrates with pathologically relevant stiffness upregulate the IKCa channel expression to enhance intracellular Ca2+ signaling and subsequent activation of the ERK signal pathway to drive cell proliferation. These findings provide a novel mechanism by which vascular stiffening regulates VSMC function.

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Section: Introductionmentioning

confidence: 99%

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IK_Ca channel‐dependent Ca²⁺ signaling

Jia

Yang

Gao

et al. 2021

Journal Cellular Physiology

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“…Consistently, western blotting and RT-qPCR showed increased expression of osteogenic differentiation markers, including ALP, RUNX2, and Col1 in the mechanical stretch group (Figures 3(f) and 3(g) ). Ion channels residing in membrane structures of cells were previously reported to act as mechanical sensors [ 23 , 24 ], and intracellular calcium ion was recognized as a common second messenger responding to mechanical force [ 25 , 26 ]. Thus, we measured expression levels of IP 3 R, which is a calcium channel residing in the ER membrane [ 13 , 14 ].…”

Section: Resultsmentioning

confidence: 99%

Gli1+ Cells Residing in Bone Sutures Respond to Mechanical Force via IP3R to Mediate Osteogenesis

Huang¹,

Liu

Wu³

et al. 2021

Stem Cells International

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Early orthodontic correction of skeletal malocclusion takes advantage of mechanical force to stimulate unclosed suture remodeling and to promote bone reconstruction; however, the underlying mechanisms remain largely unclear. Gli1+ cells in maxillofacial sutures have been shown to participate in maxillofacial bone development and damage repair. Nevertheless, it remains to be investigated whether these cells participate in mechanical force-induced bone remodeling during orthodontic treatment of skeletal malocclusion. In this study, rapid maxillary expansion (RME) mouse models and mechanical stretch loading cell models were established using two types of transgenic mice which are able to label Gli1+ cells, and we found that Gli1+ cells participated in mechanical force-induced osteogenesis both in vivo and in vitro. Besides, we found mechanical force-induced osteogenesis through inositol 1,4,5-trisphosphate receptor (IP3R), and we observed for the first time that inhibition of Gli1 suppressed an increase in mechanical force-induced IP3R overexpression, suggesting that Gli1+ cells participate in mechanical force-induced osteogenesis through IP3R. Taken together, this study is the first to demonstrate that Gli1+ cells in maxillofacial sutures are involved in mechanical force-induced bone formation through IP3R during orthodontic treatment of skeletal malocclusion. Furthermore, our results provide novel insights regarding the mechanism of orthodontic treatments of skeletal malocclusion.

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“…Multiple mechanical forces can drive the proliferation and differentiation of BMSCs. 15,16 According to several in vitro studies, [17][18][19] mechanical forces can also induce substantial changes in the osteoblast cytoskeleton, cell and nucleus morphology, and volume. FSS increased the expression of osteogenic genes in mesenchymal stem cells.…”

Section: Mechanosensitive Cellsmentioning

confidence: 99%

Mechanical regulation of bone remodeling

et al. 2022

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Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis; skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture. The exact mechanisms by which the body senses and transduces mechanical forces to regulate bone remodeling have long been an active area of study among researchers and clinicians. Such research will lead to a deeper understanding of bone disorders and identify new strategies for skeletal rejuvenation. Here, we will discuss the mechanical properties, mechanosensitive cell populations, and mechanotransducive signaling pathways of the skeletal system.

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A critical role of the K_Ca3.1 channel in mechanical stretch‐induced proliferation of rat bone marrow‐derived mesenchymal stem cells

Cited by 12 publications

References 23 publications

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IK_Ca channel‐dependent Ca²⁺ signaling

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IK_Ca channel‐dependent Ca²⁺ signaling

Gli1+ Cells Residing in Bone Sutures Respond to Mechanical Force via IP3R to Mediate Osteogenesis

Mechanical regulation of bone remodeling

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A critical role of the KCa3.1 channel in mechanical stretch‐induced proliferation of rat bone marrow‐derived mesenchymal stem cells

Cited by 12 publications

References 23 publications

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IKCa channel‐dependent Ca2+ signaling

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IKCa channel‐dependent Ca2+ signaling

Gli1+ Cells Residing in Bone Sutures Respond to Mechanical Force via IP3R to Mediate Osteogenesis

Mechanical regulation of bone remodeling

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Product

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A critical role of the K_Ca3.1 channel in mechanical stretch‐induced proliferation of rat bone marrow‐derived mesenchymal stem cells

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IK_Ca channel‐dependent Ca²⁺ signaling

Stimulation of vascular smooth muscle cell proliferation by stiff matrix via the IK_Ca channel‐dependent Ca²⁺ signaling