Xiaoyi Wang, He Xin, Xiaona Ning, Yubohan Zhang, Fuwei Liu, Zhouyang Zhang, Xuelian Jia, Weiwei Guo, Y. Hong, Wenquan Sui
{"title":"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","authors":"Xiaoyi Wang, He Xin, Xiaona Ning, Yubohan Zhang, Fuwei Liu, Zhouyang Zhang, Xuelian Jia, Weiwei Guo, Y. Hong, Wenquan Sui","doi":"10.1088/1748-605X/ac61fb","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Strontium-loaded titanium implant with rough surface modulates osseointegration by changing sfrp4 in canonical and noncanonical Wnt signaling pathways\",\"authors\":\"Xiaoyi Wang, He Xin, Xiaona Ning, Yubohan Zhang, Fuwei Liu, Zhouyang Zhang, Xuelian Jia, Weiwei Guo, Y. Hong, Wenquan Sui\",\"doi\":\"10.1088/1748-605X/ac61fb\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":9016,\"journal\":{\"name\":\"Biomedical materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2022-03-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical materials\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1088/1748-605X/ac61fb\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical materials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1088/1748-605X/ac61fb","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
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.
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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