Substrate-Mediated Regulation of Src Expression Drives Osteoclastogenesis Divergence

被引:1
|
作者
Hu, Bo [1 ,2 ,3 ,4 ,5 ]
Chen, Yiming [1 ,2 ,3 ,4 ,5 ]
Li, Yuman [1 ,2 ,3 ,4 ]
Deng, Chenyu [2 ,3 ,4 ,6 ]
Niu, Yuting [1 ,2 ,3 ,4 ,5 ]
Hu, Zhewen [1 ,2 ,3 ,4 ]
Li, Yao [1 ,2 ,3 ,4 ,5 ]
Sun, Shiyu [2 ,3 ,4 ,7 ]
Huang, Ying [1 ,2 ,3 ,4 ]
Deng, Xuliang [1 ,2 ,3 ,4 ]
Wei, Yan [1 ,2 ,3 ,4 ]
机构
[1] Peking Univ, Sch & Hosp Stomatol, Dept Geriatr Dent, Beijing 100081, Peoples R China
[2] Natl Ctr Stomatol, Beijing 100081, Peoples R China
[3] Natl Clin Res Ctr Oral Dis, Beijing 100081, Peoples R China
[4] Natl Engn Res Ctr Oral Biomat & Digital Med Device, Beijing 100081, Peoples R China
[5] Peking Univ, Sch & Hosp Stomatol, Dept Prosthodont, Beijing 100081, Peoples R China
[6] Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China
[7] Peking Univ, Sch & Hosp Stomatol, Dept Gen Dent, Beijing 100081, Peoples R China
基金
中国国家自然科学基金;
关键词
osteoclastogenesis; substrate; Src; cytoskeletal remodeling; oxidative phosphorylation (OXPHOS); RANKL-INDUCED OSTEOCLAST; BONE; DIFFERENTIATION; TOPOGRAPHY; MECHANISM;
D O I
10.3390/genes15091217
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background/Objectives: Glass, bone, and dentin are commonly applied substrates for osteoclast cultures; however, the impact of these substrates on osteoclastogenesis remains underexplored. This study aimed to address a significant gap in understanding how different substrates influence the process of osteoclastogenesis. Methods: RAW 264.7 cells were cultured and induced with RANKL on glass, bone, and dentin slides. Histological and molecular techniques were used to identify patterns and differences in osteoclast behavior on each substrate. Results: Osteoclasts cultured on glass slides possessed the greatest number of nuclei and the highest expression levels of ACP5 (TRAP) and CTSK, with osteoclasts on bone and dentin slides displaying progressively lower levels. Src expression was also most pronounced in osteoclasts on glass slides, with decreased levels observed on bone and dentin. This variation in Src expression likely contributed to differences in cytoskeletal remodeling and oxidative phosphorylation (OXPHOS), resulting in substrate-dependent divergences in osteoclastogenesis. Conclusions: Glass slides were the most favorable substrate for inducing osteoclastogenesis, while bone and dentin slides were less effective. The substrate-induced expression of Src played a fundamental role in shaping the phenotypic divergence of osteoclasts. These insights fill important knowledge gaps and have significant implications for the development and selection of in vitro models for bone-related diseases and drug screening platforms.
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页数:16
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