Cationic Glucan Dendrimer Gel-Mediated Local Delivery of Anti-OC-STAMP-siRNA for Treatment of Pathogenic Bone Resorption

被引：0

作者：

Yamamoto, Kenta ^{[1
,2
]}

Sawada, Shin-Ichi ^{[3
,4
]}

Shindo, Satoru ^{[2
]}

Nakamura, Shin ^{[2
]}

Kwon, Young M. ^{[5
]}

Kianinejad, Nazanin ^{[5
]}

Vardar, Saynur ^{[6
]}

Hernandez, Maria ^{[6
]}

Akiyoshi, Kazunari ^{[3
]}

Kawai, Toshihisa ^{[2
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Immunol, Kyoto 6028566, Japan

[2] Nova Southeastern Univ, Coll Dent Med, Dept Oral Sci & Translat Res, Ft Lauderdale, FL 33328 USA

[3] Kyoto Univ, Grad Sch Engn, Dept Polymer Chem, Kyoto 6050981, Japan

[4] Chiba Univ, Synergy Inst Futurist Mucosal Vaccine Res & Dev, Chiba 2608670, Japan

[5] Nova Southeastern Univ, Coll Pharm, Dept Pharmaceut Sci, Ft Lauderdale, FL 33328 USA

[6] Nova Southeastern Univ, Coll Dent Med, Dept Periodontol, Ft Lauderdale, FL 33328 USA

来源：

GELS | 2024年 / 10卷 / 06期

关键词：

cationic glycan dendrimer; drug delivery systems; regenerative medicine; OC-STAMP; siRNA; STIMULATORY TRANSMEMBRANE PROTEIN; SMALL INTERFERING RNA; CELL-CELL FUSION; DC-STAMP; OSTEOPOROSIS; NANOCARRIERS; OSTEOCLASTS; MECHANISMS; SYSTEM; RANKL;

D O I：

10.3390/gels10060377

中图分类号：

O63 [高分子化学（高聚物）];

学科分类号：

070305 ; 080501 ; 081704 ;

摘要：

Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in the context of pathogenic bone resorption. Thus, it is plausible that the suppression of OC-STAMP through a bioengineering approach could lead to the development of an effective treatment for inflammatory bone resorptive diseases with minimum side effects. Here, we synthesized two types of spermine-bearing (Spe) cationic glucan dendrimer (GD) gels (with or without C12) as carriers of short interfering RNA (siRNA) to silence OC-STAMP. The results showed that amphiphilic C12-GD-Spe gel was more efficient in silencing OC-STAMP than GD-Spe gel and that the mixture of anti-OC-STAMP siRNA/C12-GD-Spe significantly downregulated RANKL-induced osteoclastogenesis. Also, local injection of anti-OC-STAMP-siRNA/C12-GD-Spe could attenuate bone resorption induced in a mouse model of periodontitis. These results suggest that OC-STAMP is a promising target for the development of a novel bone regenerative therapy and that C12-GD-Spe gel provides a new nanocarrier platform of gene therapies for osteolytic disease.

引用

页数：14