title: Involvement of N-cadherin/β-catenin interaction in the micro/nanotopography induced indirect mechanotransduction.
abstract: Topographical modification at micro- and nanoscale is widely applied to enhance the tissue integration properties of biomaterials, but the underlying molecular mechanism is poorly understood. The biomaterial topography modulates cell functions via mechanotransduction of direct and indirect. We propose that N-cadherin may play a role in the topographically induced indirect mechanotransduction by regulating the β-catenin signaling. For confirmation, the cell functions, N-cadherin expression and β-catenin signaling activation of osteoblasts on titanium (Ti) surfaces with micro- or/and nanotopography are systemically compared with naive and N-cadherin down-regulating MC3T3-E1 cells. We find that the N-cadherin expression is reversely related to the intracellular β-catenin signaling and the N-cadherin/β-catenin signaling is modulated differentially by the micro- and nanotopography. The nanotopography significantly up-regulates the N-cadherin expression leading to lower β-catenin signaling activity and consequently depressed differentiation, whereas the microtopography down-regulates the N-cadherin expression resulting in enhanced β-catenin signaling and thus osteoblast differentiation. Artificial down-regulation of the N-cadherin expression can significantly up-regulate the β-catenin signaling and consequently enhance the osteoblast differentiation on all the Ti surfaces. The study for the first time clarifies the involvement of the N-cadherin/β-catenin interaction in the micro/nanotopography induced indirect mechanotransduction and provides a potentially new approach for biomaterial modification and biofunctionalization by down-regulating the cell N-cadherin expression to achieve improved clinical performance.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Stomatology, The 463 Hospital of People's Liberation Army, No. 46 XiaoHeYan Road, Shenyang 110042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China. Electronic address: zhaolingzhou1983@hotmail.com.
authors.forename: Lingzhou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Song
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China. Electronic address: wqtzym@fmmu.edu.cn.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014025:Titanium / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D015820:Cadherins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D014025:Titanium; D051176:beta Catenin; D000099200:Scaffold Protein ILK
keywords: MC3T3-E1; Mechanotransduction; Micro/nanotopography; N-cadherin; β-catenin