Long non‑coding RNA XIST inhibits osteoblast differentiation and promotes osteoporosis via Nrf2 hyperactivation by targeting CUL3

Chen,Xiao; Ma,Fengyu; Zhai,Ning; Gao,Feng; Cao,Guijun

doi:10.3892/ijmm.2021.4970

Long non‑coding RNA XIST inhibits osteoblast differentiation and promotes osteoporosis via Nrf2 hyperactivation by targeting CUL3

Authors:
- Xiao Chen
- Fengyu Ma
- Ning Zhai
- Feng Gao
- Guijun Cao
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Affiliations: Department of Spinal Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China, Department of Spine Surgery, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Imaging Department, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China
Published online on: May 24, 2021 https://doi.org/10.3892/ijmm.2021.4970
Article Number: 137
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoporosis (OP) is a common skeletal disorder characterized by a low bone mass and the deterioration of bone structure. Long non‑coding (lnc)RNA X inactive‑specific transcript (XIST) is highly expressed in the serum and monocytes of patients with OP. Thus, the purpose of the present study was to explore the mechanisms underlying the role of XIST in the progression of OP. To establish animal models of OP, female rats underwent a bilateral ovariectomy. The bone mineral density of individual rats was measured using dual‑energy X‑ray absorptiometry. The combination of XIST and cullin‑3 (CUL3) was analyzed using a dual‑luciferase reporter assay. Bone histopathological changes were assessed by hematoxylin and eosin staining. Alkaline phosphatase activity was examined by ALP staining. Finally, a series of functional experiments were performed to examine the effects of XIST on cellular behaviors. In the present study, XIST promoted OP and inhibited bone formation by regulating the expression levels of CUL3 and nuclear factor erythroid 2‑related factor 2 (Nrf2) in the rats with OP. Moreover, XIST directly targeted CUL3 and negatively regulated its expression. Of note, CUL3 downregulation reversed the effects of XIST silencing on cell viability, differentiation and mineralization, as well as the expression of Nrf2 and CUL3 in MC3T3‑E1 cells. Collectively, XIST was demonstrated to inhibit the differentiation of osteoblasts and promote OP by inhibiting the degradation of Nrf2 via targeting CUL3.

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