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Surface topography regulates osteogenic differentiation of MSCs via crosstalk between FAK/MAPK and ILK/#catenin pathways in a hierarchically porous environment Haoyi Niu, Dan Lin, Wei Tang, Yifan Ma, Bing Duan, Yuan Yuan, and Changsheng Liu ACS Biomater. Sci. Eng., Just Accepted Manuscript • DOI: 10.1021/acsbiomaterials.7b00315 • Publication Date (Web): 06 Oct 2017 Downloaded from http://pubs.acs.org on October 18, 2017
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ACS Biomaterials Science & Engineering
Surface topography regulates osteogenic differentiation of MSCs via crosstalk between FAK/MAPK and ILK/β-catenin pathways in a hierarchically porous environment
Haoyi Niu1,2, Dan Lin1, Wei Tang3, Yifan Ma1, Bing Duan2, Yuan Yuan1,2*, Changsheng Liu1,2*
1
Key Laboratory for Ultrafine Materials of Ministry of Education and The State Key
Laboratory of Bioreactor Engineering, East China University of Science and Technology,
Shanghai 200237, PR China 23
Engineering Research Center for Biomaterials of Ministry of Education, East China
University of Science and Technology, Shanghai 200237, PR China
Full mailing address of authors: East China University of Science and Technology, 130
Meilong Road, Shanghai 200237, PR China
Email address of the corresponding author:
[email protected] (Yuan Yuan);
[email protected] (Changsheng Liu)
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Abstract:
The response of mesenchymal stem cell (MSCs) to elaborate micro-architectured
topographies in three-dimensional environment and the underlying molecular mechanism
remain poorly understood. Here, with hierarchical mesoporous bioactive glass (MBG)
scaffolds as substrate model, we show the effects of specific, elaborate micro-textured
topographies (micrograiny, microporous and hybrid micrograiny/microporous surface) on
MSCs osteogenesis and the molecular mechanism involved. With a similar size and density,
the microporous surface was more favorable for the MSCs osteogenesis, and the hybrid
micrograiny/microporous surface exhibited a synergetic effect. All the micro-scaled
topographies facilitated expression of integrin subunits, focal adhesion complexes and
up-regulated FAK/MAPK and ILK/β-catenin signaling pathways. Separately blocking
FAK/MAPK and ILK/β-catenin cascade dramatically attenuated the heightened β-catenin
signaling, and the phosphorylation of ERK1/2 and P38, respectively, indicating a typical
crosstalk between FAK/MAPK and ILK/β-catenin signalings was involved. Correlating the
MSCs response with the specific topographical cues, it can be inferred that the
micrograiny/microporous topographies induced FAs assembly and homeostasis, and thus
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ACS Biomaterials Science & Engineering
FAK/MAPK and ILK/β-catenin signalings played critical role in regulating MSCs osteogenic
differentiation. The findings, therefore, have significant implications in better understanding
of the MSCs fate in a 3D environment and provided guidance of the development of novel
biomaterial for bone regeneration.
Keywords: micrograiny/microporous topography, indirect mechanotransduction, signaling
crosstalk, MSCs osteogenic differentiation
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1. Introduction
A great increase of bone defects caused by disease, trauma, together with multiple limitations
associated with the autografts, have imperatively raised the request for synthetic bone
substitutes in recent years
1-2
. It is becoming increasingly clear that a crucial event in bone
regeneration process is to in situ create a favorable extracellular microenvironment for
triggering the differentiation of mesenchymal stem cells (MSCs) into bone-forming
osteoblasts, which directly participate in subsequent formation and maturation of bone tissue 3-4
. Therefore, understanding how a MSC perceives the surrounding micro-environmental
cues and then initiates an osteogenic transformation is critical for design of the bone
substitutes. Although, the substrate-mediated osteogenesis is a complex process, micro-scales
topographical cues (0.5-10 µm) is considered as the most attractive and effective strategy to regulate this process and ultimately determine the long-term performance of material in vivo 3, 5-13
. Seo et al.’s
9
and Li Z’s studies 5, for example, found that osteogenic differentiation of
MSC was up-regulated by tailor-made micropit and micro-pillar surfaces respectively.
Moreover, several studies have shown that incorporation of microporosity (
