Direct Conversion of Human Fibroblasts into Osteoblasts Triggered by Histone Deacetylase Inhibitor Valproic Acidopen access
- Authors
- Cha, Hyeonjin; Lee, Jaeyoung; Park, Hee Ho; Park, Ju Hyun
- Issue Date
- Oct-2020
- Publisher
- MDPI
- Keywords
- direct conversion; osteoblast; histone deacetylase inhibitor; valproic acid; inhibitor for activin-like kinase 5
- Citation
- APPLIED SCIENCES-BASEL, v.10, no.20, pp.1 - 13
- Indexed
- SCIE
SCOPUS
- Journal Title
- APPLIED SCIENCES-BASEL
- Volume
- 10
- Number
- 20
- Start Page
- 1
- End Page
- 13
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/187331
- DOI
- 10.3390/app10207372
- ISSN
- 2076-3417
- Abstract
- The generation of functional osteoblasts from human somatic cells could provide an alternative means of regenerative therapy for bone disorders such as osteoporosis. In this study, we demonstrated the direct phenotypic conversion of human dermal fibroblasts (HDFs) into osteoblasts by culturing them in osteogenic medium supplemented with valproic acid (VPA), a histone deacetylase (HDAC) inhibitor. HDFs cultured with the VPA in osteogenic medium exhibited expression of alkaline phosphatase and deposition of mineralized calcium matrices, which are phenotypical characteristics of functional osteoblasts. They also expressed osteoblast-specific genes such as alkaline phosphatase, osteopontin, and bone sialoprotein, which demonstrated their direct conversion into osteoblasts. In addition, co-treatment with VPA and a specific inhibitor for activin-like kinase 5 (ALK5i II) had a synergistic effect on direct conversion. It is considered that the inductive effect of VPA on the conversion into osteoblast-lineage is due to the opening of the nucleosome structure by HDAC inhibitor, which facilitates chromatin remodeling and cellular reprogramming. Our findings provide a novel insight into the direct conversion of human somatic cells into transgene-free osteoblasts with small chemical compounds, thus making bone regeneration using cellular reprogramming strategy more clinically feasible.
- Files in This Item
-
- Appears in
Collections - 서울 공과대학 > 서울 생명공학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/187331)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.