Binding-induced fibrillogenesis peptide inhibits RANKL-mediated osteoclast activation against osteoporosis.

Autor: Liang QL; College of Medicine, Southwest Jiaotong University, No. 111 Beiyiduan, Second Ring Road, Chengdu, 610031, Sichuan Province, China; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China., Xu HG; College of Medicine, Southwest Jiaotong University, No. 111 Beiyiduan, Second Ring Road, Chengdu, 610031, Sichuan Province, China; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China., Yu L; Department of Orthopaedics, The 4th Medical Center of Chinese PLA General Hospital, Jia No.17 Heishanhu Road, Beijing, 100091, China., Ding MR; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China., Li YT; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China., Qi GF; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China., Zhang K; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China., Wang L; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China. Electronic address: wanglei@nanoctr.cn., Wang H; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China. Electronic address: wanghao@nanoctr.cn., Cui X; Department of Orthopaedics, The 4th Medical Center of Chinese PLA General Hospital, Jia No.17 Heishanhu Road, Beijing, 100091, China. Electronic address: cuixuprossor@163.com.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2023 Nov; Vol. 302, pp. 122331. Date of Electronic Publication: 2023 Sep 16.
DOI: 10.1016/j.biomaterials.2023.122331
Abstrakt: Osteoporosis is primarily driven by an imbalance between bone resorption and formation, stemming from enhanced osteoclast activity during bone remodeling. At the crux of this mechanism lies the pivotal RANK-RANKL-OPG axis. In our study, we designed two binding-induced fibrillogenesis (BIF) peptides, namely BIFP and BIFY, targeting RANK and RANKL, respectively. These BIF peptides, with distinct hydrophilic and hydrophobic characteristics, assemble into nanoparticles (NPs) in aqueous solution. Through specific ligand-receptor interactions, these NPs efficiently target and bind to specific proteins, resulting in the formation of fibrous networks that effectively inhibit the RANK-RANKL associations. Experiments have confirmed the potent inhibitory effects of peptides on both osteoclast differentiation and function. Compared with the +RANKL controls, BIFP and BIFY demonstrated a more remarkable reduction in tartrate resistant acid phosphatase (TRAP)-positive cells, achieving an impressive decline of 82.8% and 70.7%, respectively. Remarkably, the administration of BIFP led to a substantial reduction in bone resorption pit area by 17.4%, compared to a significant increase of 92.4% in the +RANKL groups. In vivo experiments on an ovariectomized mouse model demonstrated that the BIFP treated group exhibited an impressive 2.6-fold elevation in bone mineral density and an astounding 4.0-fold enhancement in bone volume/total volume as against those of the PBS-treated group. Overall, BIF peptides demonstrate remarkable abilities to impede osteoclast differentiation, presenting promising prospects for the treatment of osteoporosis.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsCompeting interests: The authors filed patents pertaining to the results presented in the paper. The authors declare the following competing financial interest(s): L. W., H. W. and Q.-L.L. are the co-inventors of a pending patent. The remaining authors declare that they have no competing interests.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: