MiRNA-10b Reciprocally Stimulates Osteogenesis and Inhibits Adipogenesis Partly through the TGF-β/SMAD2 Signaling Pathway

Abstract

As the population ages, the medical and socioeconomic impact of age-related bone disorders will further increase. An imbalance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) can lead to various bone and metabolic diseases such as osteoporosis. Thus, understanding the molecular mechanisms underlying MSC osteogenic and adipogenic differentiation is important for the discovery of novel therapeutic paradigms for these diseases. miR-10b has been widely reported in tumorigenesis, cancer invasion and metastasis. However, the effects and potential mechanisms of miR-10b in the regulation of MSC adipogenic and osteogenic differentiation have not been explored. In this study, we found that the expression of miR-10b was positively correlated with bone formation marker genes ALP, RUNX2 and OPN, and negatively correlated with adipogenic markers CEBPα, PPARγ and AP2 in clinical osteoporosis samples. Overexpression of miR-10b enhanced osteogenic differentiation and inhibited adipogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) in vitro, whereas downregulation of miR-10b reversed these effects. Furthermore, miR-10b promoted ectopic bone formation in vivo. Target prediction and dual luciferase reporter assays identified SMAD2 as a potential target of miR-10b. Silencing endogenous SMAD2 expression in hADSCs enhanced osteogenesis but repressed adipogenesis. Pathway analysis indicated that miR-10b promotes osteogenic differentiation and bone formation via the TGF-β signaling pathway, while suppressing adipogenic differentiation may be primarily mediated by other pathways. Taken together, our findings imply that miR-10b acts as a critical regulator for balancing osteogenic and adipogenic differentiation of hADSCs by repressing SMAD2 and partly through the TGF-β pathway. Our study suggests that miR-10b is a novel target for controlling bone and metabolic diseases.

PPAR Gamma-Regulated MicroRNA 199a-5p Underlies Bone Marrow Adiposity in Aplastic Anemia

“…TGFBI is a TGF-β induced protein, whose role is still unclear in the multiple lineage differentiation of MSCs. This study demonstrates that TGFBI is downregulated in adipogenic differentiation of BM-MSCs and is subsequently verified as a negative regulator of adipogenesis, which is in accordance with the reported function of the TGF-β/Smad pathway in adipogenesis 36 . miR-199a-5p has also been reported to regulate ACVR1B-mediated p-Smad2/3 expression 16 .…”

The Potential Role of the NLRP3 Inflammasome Activation as a Link Between Mitochondria ROS Generation and Neuroinflammation in Postoperative Cognitive Dysfunction

“…Recent studies have identified additional signaling pathways that can regulate cytokine synthesis and release in the pathogenesis of POCD, such as TNF-α/TLR4 (Terrando et al, 2010), ATP/P2X7 (Zheng et al, 2017) and cannabinoid receptor type 2 (CB2R)-related signaling pathways (Sun et al, 2017). Additionally, certain key signaling pathways/molecules associated with the regulation of inflammation, such as AMPK, mTOR, Nur77, and miRNAs, have been demonstrated to play critical roles in chronic age-related diseases (Wei et al, 2016; Xu et al, 2017; Li et al, 2018; Zhang et al, 2018). However, the involvement of these signaling pathways/molecules in POCD remains to be explored.…”

Strontium‑containing α‑calcium sulfate hemihydrate promotes bone repair via the TGF‑β/Smad signaling pathway

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