Nucleus-targeted delivery of nitric oxide in human mesenchymal stem cells enhances osteogenic differentiation

Du Hyong Cho, Yun Jin Hwang, Jin Hee Park, Jee Young Lee, Jung Hyun Park, Inho Jo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Nitric oxide (NO) is an important gaseous signaling molecule in various physiological processes, which functions through interactions with its acceptor molecules located in organelles. NO has an extremely short half-life, making it challenging to experimentally achieve effective NO levels in organelles to study these interactions. Here we developed an organelle-specific, peptide-based NO delivery material that targets the nucleus. NO was attached to the SH group of a cysteine residue inserted into the N-terminus of a cell-penetrating peptide (CPP) conjugated to varying repeats of the nuclear localization signal (NLS), which we denoted NO-CysCPP-NLS, through S-nitrosylation. NO-CysCPP-NLS strongly induced osteogenic differentiation of mesenchymal stem cells. This delivery concept can be extended to cells other than stem cells to elucidate the effects of NO release in the nucleus. Furthermore, conjugation of NO to CysCPP fused to mitochondria- or lysosome-targeting signals can be used to deliver NO to other organelles such as mitochondria and lysosomes, respectively.

Original languageEnglish
Article number106483
JournalBioorganic Chemistry
Volume135
DOIs
StatePublished - Jun 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Keywords

  • Cell-penetrating peptide
  • Differentiation
  • Mesenchymal stem cells
  • Nitric oxide
  • Nuclear localization signal

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