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The Cell-Penetrating Peptide GV1001 Enhances Bone Formation via Pin1-Mediated Augmentation of Runx2 and Osterix Stability
- Source :
- Biomolecules, Vol 14, Iss 7, p 812 (2024)
- Publication Year :
- 2024
- Publisher :
- MDPI AG, 2024.
-
Abstract
- Peptide-based drug development is a promising direction due to its excellent biological activity, minimal immunogenicity, high in vivo stability, and efficient tissue penetrability. GV1001, an amphiphilic peptide, has proven effective as an anti-cancer vaccine, but its effect on osteoblast differentiation is unknown. To identify proteins interacting with GV1001, biotin-conjugated GV1001 was constructed and confirmed by mass spectrometry. Proteomic analyses were performed to determine GV1001’s interaction with osteogenic proteins. GV1001 was highly associated with peptidyl-prolyl isomerase A and co-immunoprecipitation assays revealed that GV1001 bound to peptidyl-prolyl cis-trans isomerase 1 (Pin1). GV1001 significantly increased alkaline phosphatase (ALP) activity, bone nodule formation, and the expression of osteogenic gene markers. GV1001-induced osteogenic activity was enhanced by Pin1 overexpression and abolished by Pin1 knockdown. GV1001 increased the protein stability and transcriptional activity of Runx2 and Osterix. Importantly, GV1001 administration enhanced bone mass density in the OVX mouse model, as verified by µCT analysis. GV1001 demonstrated protective effects against bone loss in OVX mice by upregulating osteogenic differentiation via the Pin1-mediated protein stabilization of Runx2 and Osterix. GV1001 could be a potential candidate with anabolic effects for the prevention and treatment of osteoporosis.
- Subjects :
- GV1001
biotin-conjugated GV1001
osteoblast differentiation
Pin1
Microbiology
QR1-502
Subjects
Details
- Language :
- English
- ISSN :
- 14070812 and 2218273X
- Volume :
- 14
- Issue :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f7336dcb9c644426a88c8ff5bdc2905a
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/biom14070812