Effects of irisin on osteoblast apoptosis and osteoporosis in postmenopausal osteoporosis rats through upregulating Nrf2 and inhibiting NLRP3 inflammasome

Lili Xu; Liyan Shen; Xiaolong Yu; Peng Li; Qing Wang; Chengqian Li

doi:10.3892/etm.2019.8313

Effects of irisin on osteoblast apoptosis and osteoporosis in postmenopausal osteoporosis rats through upregulating Nrf2 and inhibiting NLRP3 inflammasome

Exp Ther Med. 2020 Feb;19(2):1084-1090. doi: 10.3892/etm.2019.8313. Epub 2019 Dec 10.

Authors

Lili Xu¹, Liyan Shen¹, Xiaolong Yu¹, Peng Li¹, Qing Wang¹, Chengqian Li¹

Affiliation

¹ Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.

Abstract

The nuclear factor E2-related factor 2 (Nrf2)/NLR family, pyrin domain containing protein 3 (NLRP3) plays an important role in osteoporosis (OP), so the effects of irisin on postmenopausal OP rats and osteoblast apoptosis through Nrf2/NLRP3 were explored in the present study. A total of 45 specific pathogen-free Sprague-Dawley rats were selected and divided into OP model group (OP group, n=15), 1 mmol/l irisin treatment group (irisin group, n=15) and normal control group (control group, n=15). After the trial period, the content of serum ALP was detected, the levels of tumor necrosis factor-α (TNF-α) in the serum and bone tissues were observed via ELISA, and the bone microstructure was observed via CT. Osteoblast apoptosis was determined through TUNEL assay, the content of apoptosis genes caspase-3 and Bcl-2, and key genes in Runt-related transcription factor 2 (Runx2), osteocalcin (OC), Nrf2 and NLRP3 was detected via RT-PCR. The protein expression of Bcl-2, Nrf2 and NLRP3 was determined via western blotting. The serum ALP level was increased in OP group compared with that in control group (P<0.05), while it declined in the irisin group. The content of TNF-α and interleukin-6 (IL-6) was significantly higher in OP group, while the content in the irisin group was close to that in the control group. The trabecular thickness, number and bone mineral density in the irisin group were all obviously larger and higher, respectively, than those in the OP group. The mRNA expression of Runx2, OC, Bcl-2 and Nrf2 in the irisin group were obviously higher (P<0.05), while that of caspase-3 and NLRP3 showed the opposite trends. The protein expression of Bcl-2 and Nrf2 in the irisin group was remarkably higher than those in the OP group, while that of NLRP3 was the opposite. irisin can upregulate Nrf2, inhibit NLRP3 inflammasome and lower the content of inflammatory factors, thereby suppressing osteoblast apoptosis in postmenopausal OP rats and reducing the incidence of postmenopausal OP.

Keywords: NLRP3 inflammasome; Nrf2; apoptosis; irisin; postmenopausal osteoporosis; rats.