Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis

Abstract

Osteoporosis, a common systematic bone homeostasis disorder related disease, still urgently needs innovative treatment methods. Several natural small molecules were found to be effective therapeutics in osteoporosis. In the present study, quercetin was screened out from a library of natural small molecular compounds by a dual luciferase reporter system. Quercetin was found to upregulate Wnt/β-catenin while inhibiting NF-κB signaling activities, and thereby rescuing osteoporosis-induced tumor necrosis factor alpha (TNFα) impaired BMSCs osteogenesis. Furthermore, a putative functional lncRNA, Malat1, was shown to be a key mediator in quercetin regulated signaling activities and TNFα-impaired BMSCs osteogenesis, as mentioned above. In an ovariectomy (OVX)-induced osteoporosis mouse model, quercetin administration could significantly rescue OVX-induced bone loss and structure deterioration. Serum levels of Malat1 were also obviously rescued in the OVX model after quercetin treatment. In conclusion, our study demonstrated that quercetin could rescue TNFα-impaired BMSCs osteogenesis in vitro and osteoporosis-induced bone loss in vivo, in a Malat1-dependent manner, suggesting that quercetin may serve as a therapeutic candidate for osteoporosis treatment.

Mechanism of Liuwei Dihuang Pills in treating osteoporosis based on network pharmacology

“…[ 37 ] Studies have shown that reducing the expression of TNF-α can increase the bone mineral density of OVX mice and promote the osteogenic differentiation of bone marrow mesenchymal stem cells. [ 38 ] CASP-3 is a crucial molecule involved in the degradation stage of apoptosis and is a promising target for treating OP. Liu et al discovered that increasing the expression of CASP-3 reduced apoptosis of osteoblasts in mice and lowered the expression of osteogenic indicators such as ALP, P1NP, and osteocalcin.…”