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表面粗糙的锶负载钛植入物通过改变经典和非经典Wnt信号通路中的sfrp4来调节骨整合

IF 3.9 3区医学 Q2 ENGINEERING, BIOMEDICAL

Biomedical materials Pub Date : 2022-03-29 DOI:10.1088/1748-605X/ac61fb

Xiaoyi Wang, He Xin, Xiaona Ning, Yubohan Zhang, Fuwei Liu, Zhouyang Zhang, Xuelian Jia, Weiwei Guo, Y. Hong, Wenquan Sui

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引用次数: 1

摘要

粗糙的形态和锶（Sr）可以激活Wnt通路来调节骨髓间充质干细胞（rBMSCs）的成骨分化，但其机制尚不清楚。我们构建了光滑的Ti（ST）表面、经过氢氟酸蚀刻的粗糙的Ti（RT）表面、经磁控溅射的载有锶的光滑Ti（ST-Sr）表面和经过锶的粗糙Ti（RT-Str）表面。我们通过碱性磷酸酶测定、茜素红染色和聚合酶链式反应（PCR）系统地研究了rBMSCs在这四个表面上的体外成骨分化。我们还研究了由sfrp4调节的经典和非经典Wnt信号通路的串扰是否是在成骨分化的不同阶段通过PCR对rBMSCs的潜在机制。我们通过体内sfrp4-siRNA测试证实了sfrp4的作用。rBMSCs的体外成骨分化按RT-Sr、RT、ST-Sr和ST的顺序降低。在机制方面，粗糙形态和Sr都增强了促进骨整合的经典Wnt途径。此外，粗糙形态学可以抑制sfrp4激活非经典Wnt通路，然后，在成骨分化的早期阶段，激活的非经典Wnt通路可以抑制经典Wnt途径。Sr持续增强sfrp4以抑制经典Wnt途径，而不是激活非经典Wnt通路。有趣的是，粗糙形态对sfrp4的作用从抑制变为增强，Sr对sfrp4的增强作用逐渐减弱。体内sfrp4-siRNA测试结果显示，骨整合按RT-Sr、RT-Sr-siRNA和ST的顺序减少。我们的结果表明，缺乏sfrp4可以抑制骨整合，表明在rBMSCs对粗糙形态和Sr的反应过程中，sfrp4是经典和非经典Wnt途径的关键调节分子。

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Strontium-loaded titanium implant with rough surface modulates osseointegration by changing sfrp4 in canonical and noncanonical Wnt signaling pathways

A rough morphology and strontium (Sr) can activate the Wnt pathway to regulate bone mesenchymal stem cells (rBMSCs) osteogenic differentiation, but the mechanism remains unclear. We constructed smooth Ti (ST) surfaces, rough Ti (RT) surfaces subjected to hydrofluoric acid etching, strontium-loaded smooth Ti (ST-Sr) surfaces subjected to magnetron sputtering, and rough strontium-loaded Ti (RT-Sr) surfaces. We systematically studied the in vitro osteogenic differentiation of rBMSCs on these four surfaces by alkaline phosphatase measurement, Alizarin Red staining and polymerase chain reaction (PCR). We also investigated whether crosstalk of the canonical and noncanonical Wnt signaling pathways regulated by sfrp4, which is an inhibitor of canonical and noncanonical Wnt, is the underlying mechanism via PCR on rBMSCs in different stages of osteogenic differentiation. We confirmed the effect of sfrp4 through an in vivo sfrp4-siRNA test. The in vitro osteogenic differentiation of rBMSCs decreased in the order RT-Sr, RT, ST-Sr, and ST. Regarding the mechanism, rough morphology and Sr both enhanced the canonical Wnt pathway to promote osseointegration. Additionally, rough morphology can inhibit sfrp4 to activate the noncanonical Wnt pathway, and then, the activated noncanonical Wnt pathway can suppress the canonical Wnt pathway at the early stage of osteogenic differentiation. Sr continuously enhanced sfrp4 to inhibit the canonical Wnt pathway instead of activating the noncanonical Wnt pathway. Interestingly, the effect of rough morphology on sfrp4 changed from inhibition to enhancement, and the enhancing effect of Sr on sfrp4 was gradually attenuated. The results of the in vivo sfrp4-siRNA test showed that osseointegration decreased in the order RT-Sr, RT-Sr-siRNA, and ST. Our results suggest that the lack of sfrp4 could suppress osseointegration, indicating that sfrp4 acts as a crucial regulatory molecule for the canonical and noncanonical Wnt pathways during the response of rBMSCs to rough morphology and Sr.

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来源期刊

Biomedical materials

Biomedical materials 工程技术-材料科学：生物材料

CiteScore

6.70

自引率

7.50%

发文量

294

审稿时长

3 months

期刊介绍： The goal of the journal is to publish original research findings and critical reviews that contribute to our knowledge about the composition, properties, and performance of materials for all applications relevant to human healthcare. Typical areas of interest include (but are not limited to): -Synthesis/characterization of biomedical materials- Nature-inspired synthesis/biomineralization of biomedical materials- In vitro/in vivo performance of biomedical materials- Biofabrication technologies/applications: 3D bioprinting, bioink development, bioassembly & biopatterning- Microfluidic systems (including disease models): fabrication, testing & translational applications- Tissue engineering/regenerative medicine- Interaction of molecules/cells with materials- Effects of biomaterials on stem cell behaviour- Growth factors/genes/cells incorporated into biomedical materials- Biophysical cues/biocompatibility pathways in biomedical materials performance- Clinical applications of biomedical materials for cell therapies in disease (cancer etc)- Nanomedicine, nanotoxicology and nanopathology- Pharmacokinetic considerations in drug delivery systems- Risks of contrast media in imaging systems- Biosafety aspects of gene delivery agents- Preclinical and clinical performance of implantable biomedical materials- Translational and regulatory matters

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