title: Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation.
abstract: Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC) differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif), a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.
authors.affiliation: Division of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Division of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Jun-Ha
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Division of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: A Rum
authors.initials: AR
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Hang Jun
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
authors.affiliation: School of Mechanical Engineering, College of Engineering, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Joong Yull
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Hong
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D044085:Microfluidics; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D012234:Rho Factor / Q000378:metabolism; D033081:Shear Strength; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D020741:rho GTP-Binding Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012234:Rho Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D020741:rho GTP-Binding Proteins