Long non-coding RNA taurine upregulated gene 1 is downregulated in osteoporosis and influences the osteogenic differentiation of bone marrow mesenchymal stem cells

Abstract

Background With aging, an imbalance in bone remodeling leading to increased bone resorption and decreased bone formation is thought to contribute to osteoporosis. Osteoblastic differentiation of bone marrow mesenchymal stem cells (BMMSCs) plays a vital role in the pathogenesis of osteoporosis. However, the detailed molecular mechanisms of osteoporosis remain incompletely understood. Given that long non-coding RNA taurine upregulated gene 1 (lnc TUG1) plays a critical role in the osteogenic differentiation, and microRNA-23b (miR-23b) as a putative sponge for lnc TUG1 has upregulated expression in osteoporosis. Therefore, this study investigated the roles of TUG1/miR-23b in osteoporotic pathology. Material and Methods TUG1 and miR-23b expression in the plasma of osteoporotic patients were evaluated by quantitative real-time PCR (qRT-PCR). The osteogenic differentiation in human BMMSCs was evaluated by qRT-PCR, western blot, Alizarin red staining after knockdown of TUG1 by small interfering RNA (siRNA) treatment. Results Decreased expression of TUG1 and increased expression of miR-23b evident in the plasma of patients with osteoporosis than in that of age- and sex-matched healthy controls. Additionally, increased miR-23b expression inhibited runt-related transcription factor 2 (RUNX2), osteocalcin, and osteopontin expression and reduced calcified nodule formation based on the results of qRT-PCR, western blot, and Alizarin Red S staining. Conclusion The study for the first time reported that silence of lncRNA TUG1 significantly suppressed the osteogenic differentiation of BMMSCs possibly by targeting the miR-23b/RUNX2 signaling pathway. This mechanism of TUG1/miR-23b/RUNX2 signaling within the osteogenic differentiation of BMMSCs might provide new insight for the development of lncRNA-directed diagnostic and therapeutic strategies for osteoporosis.

Silencing lncRNA TUG1 inhibits osteo/odontogenic differentiation of human dental pulp stem cells through the Wnt/β-catenin signaling pathway

“…In addition, recent studies have demonstrated the important role of TUG1 in osteogenic differentiation. For insurance, Teng et al found that the TUG1 was downregulated in osteoporosis and affected the osteogenesis of BMSCs [9]. TUG1 also promoted osteoblast differentiation by sponging miR-204-5p [25].…”

“…Recently, emerging evidence suggested that TUG1 was crucial to osteogenic lineage commitment of several mesenchymal stem cells (MSCs) [9][10][11]. TUG1 expression levels are downregulated in patients with osteoporosis, suggesting possible involvement in osteogenesis [9]. Another study revealed that TUG1 functioned as a positive regulator in osteogenic differentiation of BMSCs through the AMPK/mTOR/autophagy pathway [11].…”

Astragaloside positively regulated osteogenic differentiation of pre-osteoblast MC3T3-E1 through PI3K/Akt signaling pathway

“…RUNX2 is the earliest and most specific marker gene in the process of bone formation. RUNX2 also serves as a marker for osteoblasts differentiation [ 29 ]. The RUNX2 homozygous knockout mice correlated with rib aplasia [ 30 , 31 ].…”

The management of bone defect using long non-coding RNA as a potential biomarker for regulating the osteogenic differentiation process

“…Further research demonstrated that lncRNA TUG1 accelerates the osteoblasts differentiation by sponging miR-545-3p and increasing CNR2 expression [ 41 ]. Teng, Z., et al [ 42 ] verified lncRNA TUG1/miR-23b/Runx2 signaling prompt the osteogenic differentiation of BMSCs, it might provide a new insight for the diagnostic and therapeutic strategies for osteoporosis. Moreover, lncRNA TUG1 also down-regulated bFGF protein expression for the osteogenic capacity of TSPCs by promoting bFGF ubiquitination [ 43 ].…”