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通过电荷/iNOS信号通路,聚合物植入物上的带正电荷叔胺上调骨髓间充质干细胞的成骨作用。

Upregulation of BMSCs osteogenesis by positively-charged tertiary amines on polymeric implants via charge/iNOS signaling pathway.

作者信息

Zhang Wei, Liu Na, Shi Haigang, Liu Jun, Shi Lianxin, Zhang Bo, Wang Huaiyu, Ji Junhui, Chu Paul K

机构信息

Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Stomatology Department of the General Hospital of Chinese PLA, 28 FuXing Road, Beijing 100853, China.

出版信息

Sci Rep. 2015 Mar 20;5:9369. doi: 10.1038/srep09369.

DOI:10.1038/srep09369
PMID:25791957
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4366815/
Abstract

Positively-charged surfaces on implants have a similar potential to upregulate osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) as electromagnetic therapy approved for bone regeneration. Generally, their osteogenesis functions are generally considered to stem from the charge-induced adhesion of extracellular matrix (ECM) proteins without exploring the underlying surface charge/cell signaling molecule pathways. Herein, a positively-charged surface with controllable tertiary amines is produced on a polymer implant by plasma surface modification. In addition to inhibiting the TNF-α expression, the positively-charged surface with tertiary amines exhibits excellent cytocompatibility as well as remarkably upregulated osteogenesis-related gene/protein expressions and calcification of the contacted BMSCs. Stimulated by the charged surface, these BMSCs display high iNOS expressions among the three NOS isoforms. Meanwhile, downregulation of the iNOS by L-Can or siRNA inhibit osteogenic differentiation in the BMSCs. These findings suggest that a positively-charged surface with tertiary amines induces osteogenesis of BMSCs via the surface charge/iNOS signaling pathway in addition to elevated ECM protein adhesion. Therefore, creating a positively-charged surface with tertiary amines is a promising approach to promote osseointegration with bone tissues.

摘要

植入物上带正电荷的表面具有与已获批准用于骨再生的电磁疗法类似的上调骨髓间充质干细胞(BMSC)成骨作用的潜力。一般来说,它们的成骨功能通常被认为源于电荷诱导的细胞外基质(ECM)蛋白黏附,而未探究潜在的表面电荷/细胞信号分子途径。在此,通过等离子体表面改性在聚合物植入物上制备了一种叔胺可控的带正电荷表面。除了抑制TNF-α表达外,带叔胺的带正电荷表面还表现出优异的细胞相容性,以及显著上调的成骨相关基因/蛋白表达和与所接触的BMSC的钙化。受带电表面刺激,这些BMSC在三种一氧化氮合酶(NOS)同工型中显示出高诱导型一氧化氮合酶(iNOS)表达。同时,L-瓜氨酸(L-Can)或小干扰RNA(siRNA)对iNOS的下调抑制了BMSC中的成骨分化。这些发现表明,带叔胺的带正电荷表面除了增强ECM蛋白黏附外,还通过表面电荷/iNOS信号通路诱导BMSC的成骨作用。因此,制备带叔胺的带正电荷表面是促进与骨组织骨整合的一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/642b8e2fe4a4/srep09369-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/8ebee2bd21f4/srep09369-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/832b8d27704a/srep09369-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/334f3b5854b0/srep09369-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/526eb351f03f/srep09369-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/642b8e2fe4a4/srep09369-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/8ebee2bd21f4/srep09369-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/0ca56b929f4d/srep09369-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/1646b8ad9f5c/srep09369-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/832b8d27704a/srep09369-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/334f3b5854b0/srep09369-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/526eb351f03f/srep09369-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80b8/4366815/642b8e2fe4a4/srep09369-f7.jpg

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