LncRNA-KCNQ1OT1: A Potential Target in Exosomes Derived From ADSCs for The Treatment of Osteoporosis

Abstract

Background Osteoporosis is a worldwide medical and socioeconomic threat characterized by systemic impairment to bone strength and microstructure. Exosomes derived from adipose-derived stem cells (ADSCs-Exos) have been confirmed to play effective roles in the repair of various tissues and organs. This study aimed to investigate the role of ADSCs-Exos and a noval long none coding RNAKCNQ1OT1 (lnc-KCNQ1OT1) played in osteoporosis as well as the underlying mechanism. Methods MC3T3-E1 cells were treated with different doses of TNF-α (0, 1, 2.5, 5, 10 ng/ml) and then co-cultured with ADSCs-Exos or exosomes-derived from lnc-KCNQ1OT1-modified ADSCs (KCNQ1OT1-Exos). The expression of microRNA (miRNA)-141-5p (miR-141-5p) and lnc-KCNQ1OT1 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of cleaved-caspase-3, caspase-3 and Bax was determined by Western blot. Cell viability and apoptosis were assessed by cell counting kit 8 (CCK-8) and flow cytometry analysis, respectively. The binding sites between KCNQ1OT1 and miR-141-5p were validated by dual-luciferase reporter assay. Results Tumor necrosis factor-α (TNF-α) dose dependently increased miR-141-5p expression, inhibited viability and promoted apoptosis of MC3T3-E1 cells. However, miR-141-5p silencing or co-culture with ADSCs-Exos attenuated these effects. In addition, KCNQ1OT1-Exos could more significantly attenuate the induced cytotoxicity and apoptosis compared to ADSCs-Exos. Moreover, miR-141-5p was confirmed as the target of lnc-KCNQ1OT1 by luciferase reporter assay. Conclusions ADSCs-Exos attenuated cytotoxicity and apoptosis of TNF-α-induced MC3T3-E1 cells. KCNQ1OT1-Exos had a more significant inhibitory effect compared to ADSCs-Exos by the function of sponging miR-141-5p, suggesting that KCNQ1OT1-Exos could be promising agents in osteoporosis treatment.

Research Progress of Exosomes in Bone Diseases: Mechanism, Diagnosis and Therapy

“…AMSC-derived exosomes. Previous studies showed that AMSC-derived exosomes could inhibit the activation of NLRP3 inflammasome in osteoclasts and reduce the apoptosis of osteoblasts to relieve OP ( Ren et al, 2019 ; Wang S. et al, 2021 ; Zhang L. et al, 2021 ). Furthermore, Yang S. et al (2020) demonstrated that miR-130a-3p played a vital role in determining the osteogenic differentiation of AMSCs-derived exosomes.…”