Seong Semun, Vijayan Veena, Kim Jung Ha, Kim Kabsun, Kim Inyoung, Cherukula Kondareddy, Park In-Kyu, Kim Nacksung
Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
Hard-Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea.
Biomater Sci. 2023 Mar 28;11(7):2581-2589. doi: 10.1039/d2bm02038f.
CrkII, a member of the adaptor protein family, is known to participate in bone homeostasis the regulation of osteoclasts and osteoblasts. Therefore, silencing would beneficially impact the bone microenvironment. In this study, siRNA encapsulated by a bone-targeting peptide (AspSerSer)-liposome was evaluated for its therapeutic applications using a receptor activator of nuclear factor kappa-B ligand (RANKL)-induced bone loss model. (AspSerSer)-liposome- maintained its gene-silencing ability in both osteoclasts and osteoblasts and significantly reduced osteoclast formation while increasing osteoblast differentiation . Fluorescence image analyses showed that the (AspSerSer)-liposome- was present largely in bone, where it remained present for up to 24 hours and was cleared by 48 hours, even when systemically administrated. Importantly, microcomputed-tomography revealed that bone loss induced by RANKL administration was recovered by systemic administration of (AspSerSer)-liposome-. Collectively, the findings of this study suggest that (AspSerSer)-liposome- is a promising therapeutic strategy for the development of treatments for bone diseases, as it overcomes the adverse effects derived from ubiquitous expression bone-specific delivery of siRNA.
衔接蛋白家族成员CrkII已知参与骨稳态以及破骨细胞和成骨细胞的调节。因此，使其沉默将对骨微环境产生有益影响。在本研究中，使用核因子κB受体活化因子配体（RANKL）诱导的骨质流失模型，评估了由骨靶向肽（AspSerSer）-脂质体包裹的CrkII siRNA的治疗应用。（AspSerSer）-脂质体在破骨细胞和成骨细胞中均保持其基因沉默能力，并显著减少破骨细胞形成，同时增加成骨细胞分化。荧光图像分析表明，即使通过全身给药，（AspSerSer）-脂质体也主要存在于骨中，在骨中可保持长达24小时，并在48小时后清除。重要的是，显微计算机断层扫描显示，通过全身给药（AspSerSer）-脂质体可恢复RANKL给药诱导的骨质流失。总体而言，本研究结果表明，（AspSerSer）-脂质体是一种有前景的治疗策略，可用于开发骨疾病治疗方法，因为它克服了siRNA普遍表达带来的不利影响，并实现了骨特异性递送。
