Preliminary study of the homeostatic regulation of osseointegration by nanotube topology
作者全名：Chen, Tao; Ren, Mingxing; Li, Yuzhou; Jing, Zheng; Xu, Xinxin; Liu, Fengyi; Mo, Dingqiang; Zhang, Wenxue; Zeng, Jie; Zhang, He; Ji, Ping; Yang, Sheng
作者地址：[Chen, Tao; Ren, Mingxing; Li, Yuzhou; Jing, Zheng; Xu, Xinxin; Liu, Fengyi; Mo, Dingqiang; Zhang, Wenxue; Zeng, Jie; Zhang, He; Ji, Ping; Yang, Sheng] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Chen, Tao; Ren, Mingxing; Li, Yuzhou; Jing, Zheng; Xu, Xinxin; Liu, Fengyi; Mo, Dingqiang; Zhang, Wenxue; Zeng, Jie; Zhang, He; Ji, Ping; Yang, Sheng] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Chen, Tao; Ren, Mingxing; Li, Yuzhou; Jing, Zheng; Xu, Xinxin; Liu, Fengyi; Mo, Dingqiang; Zhang, Wenxue; Zeng, Jie; Zhang, He; Ji, Ping; Yang, Sheng] Chongqing Municipal Key Lab Oral Biomed Engn, Oral Higher Educ Biomed Engn, Chongqing 401147, Peoples R China
通信作者：Zhang, H; Ji, P; Yang, S (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China.; Zhang, H; Ji, P; Yang, S (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.
来源：MATERIALS TODAY BIO
ESI学科分类：
WOS号：WOS:001235503200001
JCR分区：Q1
影响因子：8.7
年份：2024
卷号：26
期号：
开始页：
结束页：
文献类型：Article
关键词：FAK; PYK2; Osteoclasts; Osteoblasts; Bone homeostasis
摘要：The ideal implant surface plays a substantial role in maintaining bone homeostasis by simultaneously promoting osteoblast differentiation and limiting overactive osteoclast activity to a certain extent, which leads to satisfactory dynamic osseointegration. However, the rational search for implant materials with an ideal surface structure is challenging and a hot research topic in the field of tissue engineering. In this study, we constructed titanium dioxide titanium nanotubes (TNTs) by anodic oxidation and found that this structure significantly promoted osteoblast differentiation and inhibited osteoclast formation and function while simultaneously inhibiting the total protein levels of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK). Knockdown of the PYK2 gene by siRNA significantly suppressed the number and osteoclastic differentiation activity of mouse bone marrow mononuclear cells (BMMs), while overexpression of PYK2 inhibited osteogenesis and increased osteoclastic activity. Surprisingly, we found for the first time that neither knockdown nor overexpression of the FAK gene alone caused changes in osteogenesis or osteoclastic function. More importantly, compared with deletion or overexpression of PYK2/FAK alone, coexpression or cosilencing of the two kinases accelerated the effects of TNTs on osteoclastic and osteogenic differentiation on the surface of cells. Furthermore, in vivo experiments revealed a significant increase in positiveexpression-PYK2 cells on the surface of TNTs, but no significant change in positiveexpression -FAK cells was observed. In summary, PYK2 is a key effector molecule by which osteoblasts sense nanotopological mechanical signals and maintain bone homeostasis around implants. These results provide a referable molecular mechanism for the future development and design of homeostasisbased regulatory implant biomaterials.
基金机构：National Natural Science Foundation of China [U23A20447, 82220108019, 82171010, 82170936, 82371018]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0098, cstc2021jcyj-jqX0028]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN202200422]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0079]; Project of Chongqing Medical University Graduate Tutor Team [cqmudstd202203]; Chongqing Scientific Research and Innovation Project for Postgraduates [CYB22216]
基金资助正文：This work was supported by the National Natural Science Foundation of China (Grant Nos. U23A20447, 82220108019, 82171010, 82170936, and 82371018) , the Natural Science Foundation of Chongqing (Grant No. cstc2021jcyj-jqX0028 CSTB2022NSCQ-MSX0098) , the Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202200422) ,the Program for Youth Innovation in Future Medicine, Chongqing Medical University (No. W0079) , the Project of Chongqing Medical University Graduate Tutor Team (cqmudstd202203) ,and the Chongqing Scientific Research and Innovation Project for Postgraduates (Grant No. CYB22216) .
