miR-149-3p Regulates the Switch between Adipogenic and Osteogenic Differentiation of BMSCs by Targeting FTO

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have been suggested to possess the capacity to differentiate into different cell lineages. Maintaining a balanced stem cell differentiation program is crucial to the bone microenvironment and bone development. MicroRNAs (miRNAs) have played a critical role in regulating the differentiation of BMSCs into particular lineage. However, the role of miR-149-3p in the adipogenic and osteogenic differentiation of BMSCs has not been extensively discovered. In this study, we aimed to detect the expression levels of miR-149-3p during the differentiation of BMSCs and investigate whether miR-149-3p participated in the lineage choice of BMSCs or not. Compared with mimic-negative control (NC), miR-149-3p mimic decreased the adipogenic differentiation potential of BMSCs and increased the osteogenic differentiation potential. Further analysis revealed that overexpression of miR-149-3p repressed the expression of fat mass and obesity-associated (FTO) gene through binding to the 3ʹ UTR of the FTO mRNA. Also, the role of miR-149-3p mimic in inhibiting adipogenic lineage differentiation and potentiating osteogenic lineage differentiation was mainly through targeting FTO, which also played an important role in regulating body weight and fat mass. In addition, BMSCs treated with miR-149-3p anti-miRNA oligonucleotide (AMO) exhibited higher potential to differentiate into adipocytes and lower tendency to differentiate into osteoblasts compared with BMSCs transfected with NC. In summary, our results detected the effects of miR-149-3p in cell fate specification of BMSCs and revealed that miR-149-3p inhibited the adipogenic differentiation of BMSCs via a miR-149-3p/FTO regulatory axis. This study provided cellular and molecular insights into the observation that miR-149-3p was a prospective candidate gene for BMSC-based bone tissue engineering in treating osteoporosis.

MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

“…BMSCs are important stromal cells in osteogenesis and metabolism [34]. It has revealed that miR-149-3p and Runx1 can reduce the adipogenic differentiation of BMSCs and enhance the osteogenic differentiation [12,35]. In SANFH, the researchers found that BMSCs had specific differentiation to adipocytes, while the differentiation to osteoblasts was basically stagnant [14].…”

“…MicroRNAs (miRNAs), as a kind of endogenous noncoding RNA, can participate in the regulation of physiological processes in various cells, including BMSCs [11]. For example, it was reported that overexpression of miR-149-3p could promote BMSC osteogenic differentiation [12]. In addition, some miRNAs have been found to be involved in the regulation of SANFH, such as miR-708 [13], miR-27a [14], and miR-195-5p [15].…”

M2 Macrophagy-derived Exosomal MiRNA-5106 Induces Bone Mesenchymal Stem Cells towards Osteoblastic Fate by Targeting Salt-inducible Kinase 2 and 3

“…Similarly, we further observed that miR-5106 was able to accelerate fracture healing in vivo. Several regulators have been reported to mediate the osteogenic differentiation of BMSCs, [33,34] with SIK2 and SIK3 genes being the two of the most important such factors. [35,36] Herein, we found that SIK2 and SIK3 were the miR-5106 target genes, thus highlighting a mechanistic role for miR-5106 in mediating osteoblastic differentiation.…”

Human and Arabidopsis alpha‐ketoglutarate‐dependent dioxygenase homolog proteins—New players in important regulatory processes

“…Removal of N 6 meA from NANOG mRNA changes the differentiation of sweat gland cells . FTO demethylation activity influences also a switch between adipogenic and osteogenic differentiation of Bone marrow‐derived mesenchymal stem cells . In later stages of growth, it sustains proper bone growth and maintains bone mass .…”