Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells
- 주제(키워드) tonsil-derived mesenchymal stem cells (TMSCs) , valproic acid (VPA) , CCN1 , osteogenesis
- 주제(기타) Cell Biology
- 설명문(일반) [Yu, Yeonsil; Oh, Se-Young; Jo, Inho] Ewha Womans Univ, Dept Mol Med, Coll Med, 25 Magokdong Ro 2 Gil, Seoul 07804, South Korea; [Yu, Yeonsil] Kangstem Biotech Co Ltd, Global Business Dev Div, 512 Teheran Ro, Seoul 06179, South Korea; [Oh, Se-Young; Jo, Inho] Ewha Womans Univ, Grad Program Syst Hlth Sci & Engn, 25 Magokdong Ro 2 Gil, Seoul 07804, South Korea; [Kim, Ha Yeong] Ewha Womans Univ, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, 1071 Anyangcheon Ro, Seoul 07985, South Korea; [Choi, Ji-Young; Jo, Sangmee Ahn] Dankook Univ, Dept Nanobiomed Sci, Cheonan 31116, South Korea; [Choi, Ji-Young; Jo, Sangmee Ahn] Dankook Univ, BK21 NBM Global Res Ctr Regenerat Med 4, Cheonan 31116, South Korea; [Choi, Ji-Young; Jo, Sangmee Ahn] Dankook Univ, Dept Pharmacol, Coll Pharm, Cheonan 31116, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190860
- 본문언어 영어
- Published As https://doi.org/10.3390/cells11030534
- PubMed https://pubmed.ncbi.nlm.nih.gov/35159343
초록/요약
Our previous study found that the level of CCN1 increases as osteogenic differentiation progresses in tonsil-derived mesenchymal stem cells (TMSCs). This study investigated how CCN1 is regulated through HDAC inhibition in TMSCs and their relationship with osteogenesis. Valproic acid (VPA) (1-5 mM), a well-known histone deacetylase (HDAC) inhibitor, strongly inhibited TMSC proliferation without altering MSC-specific surface markers, CD14, 34, 45, 73, 90 and 105. However, CD146 expression increased at 5 mM VPA. VPA increased osteogenic differentiation of TMSCs but decreased adipogenesis and chondrogenesis, as evidenced by the cell-specific staining of differentiation. The former was validated by the increased osteocalcin (OCN). The changes in CCN1 by VPA was biphasic; it increased until 48 h and decreased thereafter. Knockdown of CCN1 by using siRNA inhibited the osteogenic effect of VPA. VPA had no effect on CCN1 mRNA expression, but inhibition of protein synthesis by cycloheximide showed that VPA slowed down the CCN1 protein degradation. Moreover, overexpression of HDAC1 completely inhibited VPA-induced CCN1. Our results indicate that VPA inhibits the HDAC1, inducing CCN1 protein stability rather than gene expression, thereby promoting osteogenic differentiation of TMSCs. These findings present the noble implication of VPA as an inhibitor of HDAC1 to facilitate CCN1-induced osteogenic differentiation of MSCs.
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