RNA interference-mediated osteoprotegerin silencing increases the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio and promotes osteoclastogenesis  

作　　者：Song-Guan Wei Hui-Hong Chen Liu-Rong Xie Yuan Qin Yu-Ying Mai Lin-Hui Huang Hong-Bing Liao 

机构地区：[1]Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction,College&Hospital of Stomatology,Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China [2]Department of Stomatology,The Fourth Affiliated Hospital of Guangxi Medical University,Liuzhou 545005,Guangxi Zhuang Autonomous Region,China

出　　处：《World Journal of Stem Cells》2025年第4期64-78,共15页世界干细胞杂志(英文)

基　　金：Supported by the National Natural Science Foundation of China,No.82160192;and Guangxi Science and Technology Program,No.2023AB23037.

摘　　要：BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLU

关 键 词：OSTEOPROTEGERIN Receptor activator of nuclear factor-kappa B ligand Bone marrow-derived mesenchymal stem cells RNA interference OSTEOCLAST Bone scaffold 

分 类 号：R318[医药卫生—生物医学工程]