Dataset Information

Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis.

ABSTRACT: The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. Subsequently, miR-421-3p targeting KCNQ1OT1 was detected through a database search, and RNA fluorescent in situ hybridization, RNA immunoprecipitation, dual luciferase reporter assays all verified this relationship. Notably, KCNQ1OT1 stifled the miR-421-3p expression. The inhibition of proliferation, migration, and osteogenic differentiation caused by KCNQ1OT1 knock-down were reversed by an miR-421-3p inhibitor, further confirming the above findings. We verified that miR-421-3p specifically targeted the mammalian target of rapamycin (mTOR), and miR-421-3p inhibitor could reverse the negative effects of small interfering RNA of mTOR (si-mTOR) on MC3T3-E1 cells. Finally, osteoblasts isolated and cultured from OVX mice model and control mice also confirmed the observed trend. In combination, results mentioned above reveal that KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis.

SUBMITTER: Wang Z

PROVIDER: S-EPMC9911397 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis.

Wang Ziyu Z Zhang Hengshuo H Li Qinghui Q Zhang Lu L Chen Lu L Wang Hongliang H Chen Yunzhen Y

Scientific reports 20230209 1

The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed ...[more]

PMID: 36759677

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Project description:BackgroundPostmenopausal osteoporosis (PMOP) is the most common primary osteoporosis, which is prone to fractures and affect the health and quality of life of the elderly and even shorten their lifetime. Traditional Chinese medicine can not only effectively improve osteoporosis and reduce fracture rate, but also have tonifying and analgesic effects. The purpose of this study was to investigate the effects of Zhuanggu Zhitong (ZGZT) Capsule on autophagy related genes and proteins in PMOP rats, so as to elucidate the molecular mechanism of tonifying deficiency and regulating stasis in the treatment of osteoporosis and analgesia.MethodsThe PMOP rat model was established by bilateral oophorectomy, and then the rats were randomly divided into control group, PMOP group, PMOP + ZGZT group and PMOP + E2 group. The changes of mechanical pain threshold of rats were detected by von Frey filaments, and the changes of mechanical pain threshold of rats in each group were compared. Computed tomography (CT) and dual-energy X-ray were used to measure the bone mineral density of lumbar bone tissue. Enzyme-linked immunosorbent assay (ELISA) and tartrate-resistant acid phosphatase (TRAP) staining were used to detect inflammatory factors and bone metabolism related indicators. Hematoxylin-eosin (HE) staining was used to observe the tissue morphology of lumbar vertebra tissue. Western blot (WB) and quantitative polymerase chain reaction (qPCR) were used to detect AMPK/mTOR pathway- and autophagy-related factor expression.ResultsZGZT can effectively restore the bone mineral density (BMD) of PMOP rats, improve the microstructure of lumbar vertebra of PMOP rats, restore the balance of bone metabolism, promote the expression of AMPK and autophagy related factors, inhibit the expression of mTOR and the release of inflammatory factors, and increase the mechanical pain threshold of PMOP rats, so as to effectively improve osteoporosis and relieving osteoporosis pain in PMOP rats.ConclusionsZGZT affects autophagy by regulating AMPK/mTOR pathway, restores the homeostasis of bone metabolism and inhibits the release of inflammatory factors. Moreover, the regulation of feedback pathways between bone metabolism and inflammatory factors finally plays the role of "bone strengthening" and "pain relieving". ZGZT may be a new treatment for PMOP and relieving osteoporotic pain.

Dataset Information

Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis.

Publications

Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis.

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