Mechanical loading activates the YAP/TAZ pathway and chemokine expression in the MLO-Y4 osteocyte-like cell line

Zarka, Mylène; François, Ετιεννε; Bourmaud, Morgane; Szondi, Denis; Schwartz, Jean-Marc; Kampmann, Kristine; Hélary, Christophe; Rannou, François; Haÿ, Eric; Cohen‐Solal, Martine

doi:10.1038/s41374-021-00668-5

Cited by 20 publications

(17 citation statements)

References 61 publications

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“…The authors also showed that YAP/TAZ is crucial for TGF-β-induced matrix protease gene expression and osteocyte perilacunar/canalicular remodeling. In line with these findings, we assessed the implication of YAP/TAZ in osteocyte mechanotransduction and showed that YAP/TAZ translocated to the nucleus and activated their target genes in a 3D in vitro culture model of the MLO-Y4 osteocyte-like cell line under mechanical compression ( Zarka et al, 2021 ). YAP/TAZ silencing by short hairpin RNA partially blocked the increased M-csf and Cxcl3 gene expression induced by osteocyte loading, which suggests their role as mediators of mechanically induced chemokine expression in MLO-Y4 osteocytes.…”

Section: Yap/taz and Bone Biologymentioning

confidence: 76%

YAP/TAZ in Bone and Cartilage Biology

Zarka

Haÿ

Cohen‐Solal

2022

Front. Cell Dev. Biol.

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YAP and TAZ were initially described as the main regulators of organ growth during development and more recently implicated in bone biology. YAP and TAZ are regulated by mechanical and cytoskeletal cues that lead to the control of cell fate in response to the cellular microenvironment. The mechanical component represents a major signal for bone tissue adaptation and remodelling, so YAP/TAZ contributes significantly in bone and cartilage homeostasis. Recently, mice and cellular models have been developed to investigate the precise roles of YAP/TAZ in bone and cartilage cells, and which appear to be crucial. This review provides an overview of YAP/TAZ regulation and function, notably providing new insights into the role of YAP/TAZ in bone biology.

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Section: Yap/taz and Bone Biologymentioning

confidence: 76%

YAP/TAZ in Bone and Cartilage Biology

Zarka

Haÿ

Cohen‐Solal

2022

Front. Cell Dev. Biol.

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“…In this regard, the TAZ/YAP Hippo pathway plays an essential role in mechanosensing of alterations in cell stiffness and extracellular matrix [13][14][15][16] . Recent studies demonstrated that mechanical loading activates the TAZ/YAP pathway [25][26][27][28] and enhances TAZ/YAP nuclear translocation in response to shear stress in both bone marrow mesenchymal stem cells and MLO-Y4 osteocyte-like cell line 29,30 .…”

Section: Discussionmentioning

confidence: 99%

Genetic interactions between Polycystin-1 and TAZ in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

Cao

Smith

et al. 2023

Preprint

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Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly understood. Here, we used mouse genetics, mechanical loading, and pharmacological approaches to test the possibility that polycystin-1 and TAZ have interdependent mechanosensing functions in osteoblasts. We created and compared the skeletal phenotypes of control Pkd1flox/+;TAZflox/+, single Pkd1Oc-cKO, single TAZOc-cKO, and double Pkd1/TAZOc-cKO mice to investigate genetic interactions. Consistent with an interaction between polycystins and TAZ in bone in vivo, double Pkd1/TAZOc-cKO mice exhibited greater reductions of BMD and periosteal MAR than either single TAZOc-cKO or Pkd1Oc-cKO mice. Micro-CT 3D image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in double Pkd1/TAZOc-cKO mice compared to either single Pkd1Oc-cKO or TAZOc-cKO mice. Double Pkd1/TAZOc-cKO mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to single Pkd1Oc-cKO or TAZOc-cKO mice. Moreover, we found that double Pkd1/TAZOc-cKO mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of load-induced mechanosensing gene expression compared to control mice. Finally, control mice treated with a small molecule mechanomimetic MS2 had marked increases in femoral BMD and periosteal MAR compared to vehicle control. In contrast, double Pkd1/TAZOc-cKO mice were resistant to the anabolic effects of MS2 that activates the polycystin signaling complex. These findings suggest that PC1 and TAZ form an anabolic mechanotransduction signaling complex that responds to mechanical loading and serve as a potential novel therapeutic target for treating osteoporosis.

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“…Additionally, the concentration of intracellular calcium in MLO-Y4 was shown to significantly increase after 90 Hz of vibration for 1 h [ 43 ]. It was also previously demonstrated that mechanically stimulated osteocytes could regulate other osteoclastogenesis-inducing factors such as macrophage colony-stimulating factor (M-CSF) and C-X-C motif chemokine 10 (CXCL10) [ 44 ]. Furthermore, the migration of breast cancer cells regulated by osteoclast-derived factors has been investigated.…”

Section: Discussionmentioning

confidence: 99%

Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration

Lin

Song

et al. 2022

Cancers

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Low-magnitude (≤1 g) high-frequency (≥30 Hz) (LMHF) vibration has been shown to enhance bone mineral density. However, its regulation in breast cancer bone metastasis remains controversial for breast cancer patients and elder populations. Yoda1, an activator of the mechanosensitive Piezo1 channel, could potentially intensify the effect of LMHF vibration by enhancing the mechanoresponse of osteocytes, the major mechanosensory bone cells with high expression of Piezo1. In this study, we treated osteocytes with mono- (Yoda1 only or vibration only) or combined treatment (Yoda1 and LMHF vibration) and examined the further regulation of osteoclasts and breast cancer cells through the conditioned medium. Moreover, we studied the effects of combined treatment on breast cancer cells in regulation of osteocytes. Combined treatment on osteocytes showed beneficial effects, including increasing the nuclear translocation of Yes-associated protein (YAP) in osteocytes (488.0%, p < 0.0001), suppressing osteoclastogenesis (34.3%, p = 0.004), and further reducing migration of MDA-MB-231 (15.1%, p = 0.02) but not Py8119 breast cancer cells (4.2%, p = 0.66). Finally, MDA-MB-231 breast cancer cells subjected to the combined treatment decreased the percentage of apoptotic osteocytes (34.5%, p = 0.04) but did not affect the intracellular calcium influx. This study showed the potential of stimulating Piezo1 in enhancing the mechanoresponse of osteocytes to LMHF vibration and further suppressing breast cancer migration via osteoclasts.

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Mechanical loading activates the YAP/TAZ pathway and chemokine expression in the MLO-Y4 osteocyte-like cell line

Cited by 20 publications

References 61 publications

YAP/TAZ in Bone and Cartilage Biology

YAP/TAZ in Bone and Cartilage Biology

Genetic interactions between Polycystin-1 and TAZ in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration

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