Shear Stress Induced by an Interstitial Level of Slow Flow Increases the Osteogenic Differentiation of Mesenchymal Stem Cells through TAZ Activation

Kim, Kyung Min; Choi, Yoon Jung; Hwang, Jae Ho; Kim, A. Rum; Cho, Hang Jun; Hwang, Eun Sook; Park, Joong Yull; Lee, Sang Hoon; Hong, Jeong Ho

doi:10.1371/journal.pone.0092427

Cited by 169 publications

(135 citation statements)

References 41 publications

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“…Mechanical stress is known to stimulate MSC differentiation [163][164][165]. In general, high tensile stress is associated with tenogenesis and low tensile stress with osteogenesis, while compressive loading is associated with chondrogenesis [166].…”

Section: Mechanical Stimulationmentioning

confidence: 99%

Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors

Tellado

Balmayor

Griensven

2015

Advanced Drug Delivery Reviews

218

216

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Section: Mechanical Stimulationmentioning

confidence: 99%

Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors

Tellado

Balmayor

Griensven

2015

Advanced Drug Delivery Reviews

218

216

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“…Accumulating evidence has shown that mechanical factors, such as fluid shear stress, mechanical strain and the rigidity of the extracellular matrix, can regulate the proliferation and differentiation of BMSCs. It has been proven that both shear stress (Kim et al, 2014) and cyclic stretching (Kang et al, 2012;Kearney et al, 2010) could increase the expression of osteogenic markers. Cyclic stretching also serves as a driving factor for promoting the expression of genes related to smooth muscle cells (SMCs) in BMSCs (Hamilton et al, 2004;Park et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells

et al. 2015

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Bone marrow stromal cells (BMSCs, also broadly known as bone marrow-derived mesenchymal stem cells) are multipotent stem cells that have a self-renewal capacity and multilineage differentiation potential. Mechanical stretching plays a vital role in regulating the proliferation and differentiation of BMSCs. However, little is known about the effects of cyclic stretching on BMSC migration and invasion. In this study, using a custom-made cell-stretching device, we studied the effects of cyclic mechanical stretching on rat BMSC migration and invasion using a Transwell Boyden Chamber. The protein secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was detected by gelatin zymography, and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2) was measured by western blot. We found that cyclic mechanical stretching with 10% amplitude at 1Hz frequency for 8h promotes BMSC migration, but reduces BMSC invasion. FAK and ERK1/2 signals were activated in BMSCs after exposure to cyclic stretching. In the presence of the FAK phosphorylation blocker PF573228 or the ERK1/2 phosphorylation blocker PD98059, the cyclic-stretch-promoted migration of BMSCs was completely suppressed. On the other hand, cyclic mechanical stretching reduced the secretion of MMP-2 and MMP-9 in BMSCs, and PF573228 suppressed the cyclic-stretch-reduced secretion of MMP-2 and MMP-9. The decrease of BMSC invasion induced by mechanical stretching is partially restored by PF573228 but remained unaffected by PD98059. Taken together, these data show that cyclic mechanical stretching promotes BMSC migration via the FAK-ERK1/2 signalling pathway, but reduces BMSC invasion by decreasing secretion of MMP-2 and MMP-9 via FAK, independent of the ERK1/2 signal.

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“…The expression of Cyr61/CCN1 is known to be activated in response to mechanical stress at the transcriptional level (6) in several kinds of cells, such as fibroblasts (40), smooth muscle cells (13) in vitro, and skeletal muscle in vivo (20). With regard to bone cells and MSCs, only in vitro studies with shear stress have reported the upregulation of Cyr61/CCN1 (19,21,48). This is the first study to show the stimulated expression of Cry61/CCN1 with mechanical tensile stress in the cranial suture tissue where intramembranous ossification is under progress.…”

Section: Discussionmentioning

confidence: 99%

<b>Tensile stress stimulates the expression of osteogenic cytokines/growth factors and matricellular proteins in the mouse cranial suture at the site of osteoblast differ</b><b>entiation </b>

et al. 2016

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Mechanical stress promotes osteoblast proliferation and differentiation from mesenchymal stem cells (MSCs). Although numerous growth factors and cytokines are known to regulate this process, information regarding the differentiation of mechanically stimulated osteoblasts from MSCs in in vivo microenvironment is limited. To determine the significant factors involved in this process, we performed a global analysis of differentially expressed genes, in response to tensile stress, in the mouse cranial suture wherein osteoblasts differentiate from MSCs. We found that the gene expression levels of several components involved in bone morphogenetic protein, Wnt, and epithelial growth factor signalings were elevated with tensile stress. Moreover gene expression of some extracellular matrices (ECMs), such as cysteine rich protein 61 (Cyr61)/CCN1 and galectin-9, were upregulated. These ECMs have the ability to modulate the activities of cytokines and are known as matricellular proteins. Cyr61/CCN1 expression was prominently increased in the fibroblastic cells and preosteoblasts in the suture. Thus, for the first time we demonstrated the mechanical stimulation of Cyr61/CCN1 expression in osteogenic cells in an ex vivo system. These results suggest the importance of matricellular proteins along with the cytokine-mediated signaling for the mechanical regulation of MSC proliferation and differentiation into osteoblastic cell lineage in vivo.Mechanical stress controls bone mass by affecting recruitment of osteoprogenitors as well as osteoblast differentiation from mesenchymal stem cells (MSCs) in the bone tissue (7,8). Elucidation of the precise mechanisms involved in the osteoblastogenesis stimulated by mechanical stress, especially the mechanism for osteogenic differentiation of MSCs, will contribute to the progress of regenerative medicine for effective production of bone tissue from MSC sources. Increasing evidence has revealed that the process of mechanical stress-stimulated osteoblastogenesis is controlled by many cytokines/growth factors (9,32,34,36). Especially bone morphogenetic protein (BMP) signaling and Wnt signaling play important roles in the development of osteoblasts from MSCs (5), but the more relevant factors among these or

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Shear Stress Induced by an Interstitial Level of Slow Flow Increases the Osteogenic Differentiation of Mesenchymal Stem Cells through TAZ Activation

Cited by 169 publications

References 41 publications

Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors

Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors

Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells

<b>Tensile stress stimulates the expression of osteogenic cytokines/growth factors and matricellular proteins in the mouse cranial suture at the site of osteoblast differ</b><b>entiation </b>

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