Study on the mechanism of NLRP3 effect on the skeleton of de-ovalized mice

• Published in: Biochemistry and biophysics reports 2023-09, Vol.35, p.101496-101496, Article 101496
• Main Authors: Yang, Chenchen, Song, Bing, Han, Lixia, Gao, Zhize
• Format: Article
• Language: English
• Subjects: Inflammation; NLRP3; Osteoporosis; Ovariectomy; Pyroptosis
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2023.101496

Postmenopausal osteoporosis caused by estrogen deficiency affects millions of women worldwide. By influencing both osteoblast and osteoclast development, NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) is a key player in the etiology of osteoporosis (OP). The purpose of this research was to look into the mechanism of action of NLRP3 in osteoporosis caused by a lack of estrogen, highlighting that NLRP3 induces osteoblast pyroptosis and thus inflammatory responses in de-ovulated mice, thereby inhibiting osteogenic differentiation and participating in the development of osteoporosis. In de-ovulated mice, we found an enhanced inflammatory response and suppression of osteogenic activity. In vitro experiments, we found a significant increase in markers of cell pyroptosis and inflammatory responses and a significant decrease in markers of osteogenic differentiation in osteoblasts from de-ovulated mice. However, knockdown of the NLRP3 gene inhibited this cell pyroptosis and improved osteogenic differentiation of osteoblasts. Our findings indicate a potential therapeutic potential for the treatment of estrogen deficiency-induced osteoporosis by demonstrating the critical role that NLRP3 inflammatory vesicles and their downstream-mediated cellular pyroptosis play in bone differentiation. [Display omitted] •NLRP3 promotes inflammatory responses in de-ovulated mice.•NLRP3 is involved in the inhibition of osteogenic differentiation in de-ovalized mice.•NLRP3 promotes osteoblast pyroptosis in de-ovulated mice, leading to the release of inflammatory factors.•NLRP3 promotes osteoblast pyroptosis in de-ovalized mice, leading to inhibition of osteogenic differentiation.