LncRNA DANCR and miR-320a suppressed osteogenic differentiation in osteoporosis by directly inhibiting the Wnt/β-catenin signaling pathway

Abstract

Our study aimed to determine how lncRNA DANCR, miR-320a, and CTNNB1 interact with each other and regulate osteogenic differentiation in osteoporosis. qRT-PCR and western blotting were performed to determine the expression of DANCR, miR-320a, CTNNB1, and the osteoporosis- or Wnt/β-catenin pathway-related markers T-cell factor 1 (TCF-1), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Interactions between CTNNB1, DANCR, and miR-320a were predicted by bioinformatics approaches and validated using a luciferase assay. Osteoblastic phenotypes were evaluated by ALP staining, ALP activity assay and Alizarin Red staining. The bilateral ovariectomy method was used to establish an in vivo osteoporosis model. Bone morphological changes were examined using hematoxylin and eosin (H&E) and Alcian Blue staining. The expression levels of DANCR and miR-320a in BMSCs derived from osteoporosis patients were upregulated, whereas CTNNB1 expression was downregulated compared with that in healthy controls. Importantly, we demonstrated that miR-320a and DANCR acted independently from each other and both inhibited CTNNB1 expression, whereas the inhibitory effect was additive when miR-320a and DANCR were cooverexpressed. Moreover, we found that DANCR overexpression largely abrogated the effect of the miR-320a inhibitor on CTNNB1 expression and the Wnt/β-catenin signaling pathway in BMSCs during osteogenic differentiation. We further confirmed the results above in BMSCs derived from an osteoporosis animal model. Taken together, our findings revealed that DANCR and miR-320a regulated the Wnt/β-catenin signaling pathway during osteogenic differentiation in osteoporosis through CTNNB1 inhibition. Our results highlight the potential value of DANCR and miR-320a as promising therapeutic targets for osteoporosis treatment.

DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis

“…DANCR is a recently identified 8.3-kb lncRNA located on Chromosome 4, consisting of five exons. DANCR was revealed to repress osteogenic differentiation in osteoporosis through inhibiting β-catenin expression [30]. In addition, DANCR expression was found upregulated in circulating monocytes, and increase their bone-resorbing activities in osteoporotic patients and identified as a potential biomarker of postmenopausal osteoporosis [31].…”

Long non‑coding RNA RP11‑84C13.1 promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression via the miR‑23b‑3p/RUNX2 axis

“…Recently, emerging research has illustrated the significance of lncRNAs as important regulators in osteoclastogenesis and osteoblast differentiation. They can play a vital role by regulating cell structural integrity, controlling subcellular localization and inducing epigenetic modification (20)(21)(22). For example, lncRNA SNHG1 has been revealed to attenuate osteogenic differentiation via the miR-101/DKK1 axis in hBMSCs (23).…”

MYC Promoted The Formation of RANKL Induced Osteoclasts By Modulating The miR-320a/PTEN Axis

“…In addition, miR-320a is also a microRNA which was associated with the growth and development of osteoblasts. There is study revealed that the expression of miR-320a and lncRNA DANCR relieved the symptoms of osteoporosis by suppressing the Wnt/β-catenin pathway (Wang et al, 2020a). However, there is also study suggested that the expression of miR-320a was promoted in postmenopausal osteoporosis and miR-320a could induce the oxidative damage of osteoblasts by suppressing the PI3K/AKT signaling pathway (De-Ugarte et al, 2018; Kong et al, 2019).…”

“…In addition, miR-320a is also a microRNA which was associated with the occurrence and development of osteoporosis (Wang et al, 2020a). Moreover, the expression of miR-320a is increased in postmenopausal women with osteoporosis.…”