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Suppression of NLRP3 inflammasome improves alveolar bone defect healing in diabetic rats.

Abstract：

BACKGROUND:Excessive inflammatory response under hyperglycemia can impair alveolar bone defect healing under diabetic conditions. NLRP3 (NACHT [nucleotide-binding oligomerization], LRR [leucine-rich repeat], and PYD [pyrin domain] domains-containing protein 3) inflammasome has been considered to play a crucial role in the inflammatory response, but its correlation with the impaired alveolar bone repair in diabetes still remains unclarified. The objective of the current study is to investigate the effect of NLRP3 inflammasome inhibition by a lentiviral short hairpin RNA (shRNA) targeting NLRP3 on alveolar bone defect healing in diabetic rats. METHODS:Diabetes was induced in rats by high-fat diet and streptozotocin injection, and alveolar bone defects in both maxillae were created by surgery. Then, the lentiviral shRNA targeting NLRP3 was applied in the defect. Eight weeks after surgery, the alveolar bone regeneration was examined using hematoxylin and eosin (H&E) staining, and the gene expression in the bone healing site was detected using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis and western blot analysis. RESULTS:H&E staining showed that treatment with lentiviral shRNA targeting NLRP3 could increase the bone regeneration score in the alveolar bone defect of diabetic rats. Additionally, qRT-PCR analysis and western blot analysis of the bone defect demonstrated that this shRNA inhibited the expression of NLRP3, apoptosis-associated speck-like protein containing a CARD, caspase-1, and proinflammatory cytokine interleukin-1β and increased the expression of osteogenic markers Runt-related transcription factor 2 and osteocalcin. CONCLUSIONS:Our findings suggested that inhibition of NLRP3 inflammasome could improve alveolar bone defect healing in diabetic rats. The beneficial effect may correlate with reduced proinflammatory cytokine production and increased osteogenic gene expression in hyperglycemia.

journal_name

J Orthop Surg Res

journal_title

Journal of orthopaedic surgery and research

authors

Li H,Zhong X,Chen Z,Li W

doi

10.1186/s13018-019-1215-9

subject

Has Abstract

pub_date

2019-05-30 00:00:00

pages

167

issue

issn

1749-799X

pii

10.1186/s13018-019-1215-9

journal_volume

pub_type

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Suppression of NLRP3 inflammasome improves alveolar bone defect healing in diabetic rats.