α7-nAChR/P300/NLRP3-regulated pyroptosis mediated poor articular cartilage quality induced by prenatal nicotine exposure in female offspring rats.
Chem Biol Interact
; 400: 111183, 2024 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-39098741
ABSTRACT
Nicotine is developmentally toxic. Prenatal nicotine exposure (PNE) affects the development of multiple fetal organs and causes susceptibility to a variety of diseases in offspring. In this study, we aimed to investigate the effect of PNE on cartilage development and osteoarthritis susceptibility in female offspring rats. Wistar rats were orally gavaged with nicotine on days 9-20 of pregnancy. The articular cartilage was obtained at gestational day (GD) 20 and postnatal week (PW) 24, respectively. Further, the effect of nicotine on chondrogenic differentiation was explored by the chondrogenic differentiation model in human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). The PNE group showed significantly shallower Safranin O staining and lower Collagen 2a1 content of articular cartilage in female offspring rats. Further, we found that PNE activated pyroptosis in the articular cartilage at GD20 and PW24. In vitro experiments revealed that nicotine inhibited chondrogenic differentiation and activated pyroptosis. After interfering with nod-like receptors3 (NLRP3) expression by SiRNA, it was found that pyroptosis mediated the chondrogenic differentiation inhibition of WJ-MSCs induced by nicotine. In addition, we found that α7-nAChR antagonist α-BTX reversed nicotine-induced NLRP3 and P300 high expression. And, P300 SiRNA reversed the increase of NLRP3 mRNA expression and histone acetylation level in its promoter region induced by nicotine. In conclusion, PNE caused chondrodysplasia and poor articular cartilage quality in female offspring rats. PNE increased the histone acetylation level of NLRP3 promoter region by α7-nAChR/P300, which resulting in the high expression of NLRP3. Further, NLRP3 mediated the inhibition of chondrogenic differentiation by activating pyroptosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prenatal Exposure Delayed Effects
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Cartilage, Articular
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Rats, Wistar
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Mesenchymal Stem Cells
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Alpha7 Nicotinic Acetylcholine Receptor
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Pyroptosis
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nicotine
Limits:
Animals
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Female
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Humans
/
Pregnancy
Language:
En
Journal:
Chem Biol Interact
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Irlanda