Biochemical and Biophysical Research Communications
Long non-coding RNA, Bmcob, regulates osteoblastic differentiation of bone marrow mesenchymal stem cells
Introduction
Bone marrow mesenchymal stem cells (BMSCs) are initial cells with self-renewing, high proliferation and multiple-directional differentiation ability. They can differentiate into osteoblasts and adipocytes [1]. When BMSCs, affected by some certain factors, switch from osteogenesis towards adipogenesis, bone homeostasis will be disturbed, eventually leading to osteoporosis [1]. Thus, making sense of the underlying mechanisms behind osteoblastic differentiation of BMSCs is very meaningful to develop new therapies for osteoporosis. Long non-coding RNAs (lncRNAs) are mRNA-like transcripts with length larger than 200 nt and without capacity for protein coding [2]. Emerging evidences demonstrate that lncRNAs play a critical role in regulating BMSCs differentiation [3].
Selenoproteins are a class of selenocysteine (Sec)-containing proteins, of which many act as antioxidants through catalyzing redox reactions [4]. The incorporation of Sec into selenoproteins is complicated, because it requires identifying and recoding a UGA codon which usually functions as the stop codon [5]. Unlike the classical translation, Sec integration calls for several special transcription factors, including the selenocysteine insertion sequence (SECIS) element located in the 3′ untranslated region (3’ UTR), the SECIS binding protein 2 (SBP2), the dedicated elongation factor (eEFSec), and the selenocysteyl tRNA (Sec-tRNASec) [6]. Among the selenoproteins so far discovered, selenoprotein P (Sepp1) is the most abundant selenoprotein in serum, and the only one containing multiple Sec residues (10 in humans and mice) [7]. A study about healthy euthyroid postmenopausal women revealed that plasma concentrations of Sepp1 were positively related to bone mineral density (BMD) and inversely correlated to biomarkers of bone turnover [8]. In addition, Sepp1 is essential for selenium (Se) metabolism in bones. Due to Se transportion supported by Sepp1, bones receive priority Se supplication and thus maintain privileged Se status in Se deficiency states, like the central nervous system and several endocrine organs [9]. It had been reported that a small non-coding RNA, microRNA-7, acted as a mediator of Sepp1 expression in diverse tissues and different stages of development [7].
However, whether Sepp1 plays a role in BMSCs differentiation and whether lncRNAs regulate the expression of Sepp1 and/or other selenoproteins remain unclear. Here, we identified a novel lncRNA, Bmcob, and tried to investigated its role on osteoblastic differentiation of primary mouse BMSCs (mBMSCs).
Section snippets
Animals and cell cultures
All procedures involving mice were approved by the Animal Ethics Committee of the Central South University. All mice were kept in the specific pathogen–free facility at the Laboratory Animal Research Center at Central South University. Primary mBMSCs were isolated from the tibias and femurs of 6- to 8-week-old C57BL/6 J mice as reported previously [10]. Bone marrow cavities were flushed with culture medium, Dulbecco's Modified Eagle's Medium with low glucose (DMEM-LG, Gibco) containing 10%
Altered expression of lncRNAs and genes in primary BMSCs after osteogenic induction
To identify differentially expressed lncRNAs and encoding genes during osteogenic differentiation, we conducted microarray analysis using RNAs extracted from BMSCs cultured in medium with or without osteoblast-inducer reagents for 7 days. A total of 40 differentially expressed lncRNAs (>3.0-fold change) were identified, among which 16 were upregulated and 24 were downregulated after osteogenic induction (Fig. 1A). lncRNAs are reported to regulate transcriptional processes of neighboring coding
Discussion
The disturbed osteogenic differentiation along with the immoderate adipogenic ability of BMSCs contributes to the pathogenesis of osteoporosis [1]. Thus, studying the mechanisms determining lineage fate of BMSCs provides further possibilities for development of new therapeutics against osteoporosis. Emerging evidences showed that lncRNAs functioned as important regulators in differentiation processes of BMSCs.
In the present study, we discovered a novel lncRNA, Bmcob, which was located 109 bp
Conflicts of interest
All authors declare no conflicts of interest.
Acknowledgement
This work was supported by three National Natural Science Foundation of China (Grant NO. 81700785, 81500681, and 81500686).
References (22)
- et al.
Selenoproteins and selenium status in bone physiology and pathology
Biochim. Biophys. Acta
(2014) - et al.
Selenoproteins: antioxidant selenoenzymes and beyond
Arch. Biochem. Biophys.
(2016) - et al.
The selenium to selenoprotein pathway in eukaryotes: more molecular partners than anticipated
Biochim. Biophys. Acta
(2009) - et al.
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation
J. Clin. Invest.
(2015) - et al.
Modular regulatory principles of large non-coding RNAs
Nature
(2012) - et al.
Inhibition of lncRNA MIR31HG promotes osteogenic differentiation of human adipose-derived stem cells
Stem Cell.
(2016) - et al.
Molecular mechanism of selenoprotein P synthesis
Biochim. Biophys. Acta
(2018) - et al.
Expression and regulation of mouse selenoprotein P transcript variants differing in non-coding RNA
RNA Biol.
(2012) - et al.
Bone turnover and bone mineral density are independently related to selenium status in healthy euthyroid postmenopausal women
J. Clin. Endocrinol. Metab.
(2012) - et al.
Selenoprotein P is the essential selenium transporter for bones
Metallomics
(2014)
Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Ialpha2 expression via miR-342
Faseb. J.
Cited by (21)
New insights into the role of long non-coding RNAs in osteoporosis
2023, European Journal of PharmacologyFlexible strategy of epitaxial oxide thin films
2022, iScienceCitation Excerpt :Lastly, remote epitaxy technology could be further improved along with the development of large-scale 2D materials, which will provide an excellent platform to produce large-scale freestanding epitaxial oxide thin films. ( ii) For the aspect of functionalities, most of the current demonstrated flexible oxide films are based on single-phase materials, to realize more functionalities or multifunctionality, flexible oxide-based composite thin films are desirable, such as 0–3 type nanoparticle-in-matrix structure (Huang et al., 2018a, 2018b, 2021a, 2021b, 2021c, 2021d, 2021e; Qi et al., 2018), 1–3 type nanopillar-in-matrix structure (Huang et al., 2021a, 2021b, 2021c, 2021d, 2021e; Fan et al., 2017; Huang et al., 2021a, 2021a, 2021b, 2021b, 2021b, 2021c, 2021c, 2021c, 2021d, 2021d, 2021d, 2021e, 2021e, 2021e; Zhang et al., 2020a, 2020b), as well as 2-2 type multilayers (Huang et al., 2020a, 2020a, 2020b, 2020b, 2020b, 2020b, 2020c, 2020c, 2021a, 2021b, 2021c, 2021d, 2021e; Huang et al., 2020a, 2020b; Sun et al., 2018). In addition, the freestanding or flexible oxide films provide a perfect platform for flexoelectricity; some unique physical properties might be discovered (Cai et al., 2022; Chen et al., 2015).
Contribution of miRNAs and lncRNAs in osteogenesis and related disorders
2021, Biomedicine and PharmacotherapyCircRNAs and LncRNAs in Osteoporosis
2020, DifferentiationCitation Excerpt :LncRNA osteoblast differentiation-related lncRNA in BMSCs (Bmcob), located downstream of 3′ UTR of selenoprotein P (Sepp1) gene, was significantly upregulated during osteogenesis of mouse primary BMSCs (Sun et al., 2018). Silence of Bmcob inhibited osteogenesis of BMSCs in vitro, but its overexpression did not enhance osteogenic capacity (Sun et al., 2018). Bmcob, a critical trans-acting factor for selenoprotein synthesis, related to selenocysteine insertion sequence binding protein 2 (SBP2), possibly regulated some selenoproteins expression through controlling nucleocytoplasmic shuttling of SBP2, and eventually prevented BMSCs from oxidative stress-induced inhibition of osteogenesis (Sun et al., 2018).
Osteoporoz Epigenetiği
2023, Turk Osteoporoz Dergisi