Nicotinamide mononucleotide alleviates Aluminum induced bone loss by inhibiting the TXNIP-NLRP3 inflammasome
Autor: | Fan Jiaojiao, Qiugen Wang, Chi Zhang, Haipeng Liang, Zizheng Wu, Jian Gao, Chunlin Li, Qi Wang |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine medicine.medical_treatment Cell Cycle Proteins Pharmacology Nicotinamide adenine dinucleotide Toxicology medicine.disease_cause Cell Line Rats Sprague-Dawley Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Aluminum Chloride Animals Femur Bone Resorption Receptor Nicotinamide Mononucleotide Nicotinamide mononucleotide Chemistry Inflammasome X-Ray Microtomography 030104 developmental biology Cytokine 030220 oncology & carcinogenesis NAD+ kinase Carrier Proteins TXNIP Oxidative stress medicine.drug |
Zdroj: | Toxicology and Applied Pharmacology. 362:20-27 |
ISSN: | 0041-008X |
Popis: | Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We orally exposed AlCl3 (10 mg/L) to Sprague-Dawley rats in drinking water for 12 weeks while NMN (20 mg/kg) were intraperitoneally injected in last 4 weeks. We found that Al could induce bone damages, bone loss and oxidative stress. In addition, we showed that Al triggered inflammatory responses, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. However, NMN treatment significantly alleviated Al-induced bone injuries by decreasing bone loss, suppressing oxidative stress as well as inhibiting Thioredoxin-interacting protein (TXNIP)-NLRP3 inflammasome pathway and pro-inflammatory cytokine production in vivo and in vitro. Meanwhile, treatment with TXNIP siRNA performed the same protective effects as NMN in Al-treated MC3T3-E1 cells. Collectively, our results suggest that NMN may reduce Al-induced bone loss partly by suppression of the TXNIP-NLRP3 inflammasome pathway. |
Databáze: | OpenAIRE |
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