Format

Send to

Choose Destination
Stem Cell Res Ther. 2018 Apr 10;9(1):98. doi: 10.1186/s13287-018-0853-x.

Histone hypo-acetylation of Sox9 mediates nicotine-induced weak cartilage repair by suppressing BMSC chondrogenic differentiation.

Tie K1, Wu M2,3, Deng Y1,3, Wen Y1,3, Dan Xu4,3, Chen L5, Wang H6,7.

Author information

1
Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China.
2
Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, 430071, People's Republic of China.
3
Hubei Provincial Key Laboratory of Developmentally Originated Diseases, 185 Donghu Road, Wuchang District, Wuhan, 430071, People's Republic of China.
4
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, People's Republic of China.
5
Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China. lbchen@whu.edu.cn.
6
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, People's Republic of China. wanghui19@whu.edu.cn.
7
Hubei Provincial Key Laboratory of Developmentally Originated Diseases, 185 Donghu Road, Wuchang District, Wuhan, 430071, People's Republic of China. wanghui19@whu.edu.cn.

Abstract

BACKGROUND:

Nicotine has negative effects on tissue repair, little research concerns its effect on the cartilage repair of tissue engineering stem cells. The present study aimed to investigate the effects of nicotine on the bone marrow-derived mesenchymal stem cells' (BMSCs) chondrogenic repair function of cartilage defects and explored the molecular mechanism.

METHODS:

A cartilage defect model of rat was repaired by BMSC transplantation, and treated with nicotine or saline at 2.0 mg/kg/d in 12 weeks. Nicotine's effect on chondrogenic differentiation was studied by exposing BMSCs to nicotine at 0.1, 1, 10, and 100 μM, and methyllycaconitine (MLA), which is a selective α7-nicotinic acetylcholine receptor (nAChR) inhibitor and si-RNA of nuclear factor of activated T cells 2 (NFATc2), were used to verify the molecular mechanism of nicotine's effect.

RESULTS:

Data showed that nicotine inhibited cartilage repair function by suppressing SRY-type high-mobility group box 9 (Sox9) in regenerated tissues. Further in vitro study demonstrated that nicotine enhanced intracellular Ca2+ and activity of calcineurin (CaN) through α7-nAChR, increased the nucleic expressions of NFATc2 and the bindings to SOX9 promoter, and thus reduced the acetylation of H3K9 and H3K14 in SOX9 promoter.

CONCLUSIONS:

Findings from this study demonstrated that nicotine suppressed the chondrogenic differentiation of BMSCs in vivo and in vitro, which offers insight into the risk assessment of cartilage defect repair in a nicotine exposure population and its therapeutic target.

KEYWORDS:

Bone marrow-derived mesenchymal stem cells; Cartilage defect; Chondrogenic differentiation; Histone acetylation; Nicotine

PMID:
29631619
PMCID:
PMC5891899
DOI:
10.1186/s13287-018-0853-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center