Osteogenic CpG Oligodeoxynucleotide, iSN40, Inhibits Osteoclastogenesis in a TLR9-Dependent Manner DOI Creative Commons

R. Ikeda,

Chihaya Kimura,

Yuma Nihashi

et al.

Life, Journal Year: 2024, Volume and Issue: 14(12), P. 1572 - 1572

Published: Nov. 30, 2024

A CpG oligodeoxynucleotide (CpG-ODN), iSN40, was originally identified as promoting the mineralization and differentiation of osteoblasts, independent Toll-like receptor 9 (TLR9). Since ODNs are often recognized by TLR9 inhibit osteoclastogenesis, this study investigated dependence anti-osteoclastogenic effect iSN40 to validate its potential an osteoporosis drug. The murine monocyte/macrophage cell line RAW264.7 treated with activator nuclear factor-κB ligand (RANKL) induce osteoclast differentiation, then on quantified tartrate-resistant acid phosphatase (TRAP) staining real-time RT-PCR. completely inhibited RANKL-induced into TRAP+ multinucleated osteoclasts suppressing osteoclastogenic genes inducing anti-/non-osteoclastogenic genes. Treatment a inhibitor, E6446, or mutation in motif abolished intracellular uptake iSN40. These results demonstrate that is subcellularly internalized via motif, modulates RANKL-dependent gene expression, ultimately inhibits osteoclastogenesis. Finally, confirmed osteoclastogenesis cells cocultured osteoblast MC3T3-E1, presenting model bone remodeling. This demonstrates which exerts both pro-osteogenic effects, may be promising nucleic drug for osteoporosis.

Language: Английский

Towards Aptamer-Targeted Drug Delivery to Brain Tumors: The Synthesis of Ramified Conjugates of an EGFR-Specific Aptamer with MMAE on a Cathepsin B-Cleavable Linker DOI Creative Commons
Vladimir A. Brylev, Ekaterina V. Ryabukhina, Evgeniya V. Nazarova

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(11), P. 1434 - 1434

Published: Nov. 11, 2024

Targeted delivery of chemotherapeutic agents is a well-established approach to cancer therapy. Antibody-drug conjugates (ADCs) typically carry toxic payloads attached tumor-associated antigen-targeting IgG antibody via an enzyme-cleavable linker that releases the drug inside cell. Aptamers are promising alternative antibodies in terms antigen targeting; however, their polynucleotide nature and smaller size result completely different PK/PD profile compared IgG. This may prove advantageous: owing lower molecular weight, aptamer-drug achieve better penetration solid tumors ADCs.

Language: Английский

Citations

0
Osteogenic CpG Oligodeoxynucleotide, iSN40, Inhibits Osteoclastogenesis in a TLR9-Dependent Manner DOI Creative Commons

R. Ikeda,

Chihaya Kimura,

Yuma Nihashi

et al.

Life, Journal Year: 2024, Volume and Issue: 14(12), P. 1572 - 1572

Published: Nov. 30, 2024

A CpG oligodeoxynucleotide (CpG-ODN), iSN40, was originally identified as promoting the mineralization and differentiation of osteoblasts, independent Toll-like receptor 9 (TLR9). Since ODNs are often recognized by TLR9 inhibit osteoclastogenesis, this study investigated dependence anti-osteoclastogenic effect iSN40 to validate its potential an osteoporosis drug. The murine monocyte/macrophage cell line RAW264.7 treated with activator nuclear factor-κB ligand (RANKL) induce osteoclast differentiation, then on quantified tartrate-resistant acid phosphatase (TRAP) staining real-time RT-PCR. completely inhibited RANKL-induced into TRAP+ multinucleated osteoclasts suppressing osteoclastogenic genes inducing anti-/non-osteoclastogenic genes. Treatment a inhibitor, E6446, or mutation in motif abolished intracellular uptake iSN40. These results demonstrate that is subcellularly internalized via motif, modulates RANKL-dependent gene expression, ultimately inhibits osteoclastogenesis. Finally, confirmed osteoclastogenesis cells cocultured osteoblast MC3T3-E1, presenting model bone remodeling. This demonstrates which exerts both pro-osteogenic effects, may be promising nucleic drug for osteoporosis.

Language: Английский

Citations

0