Exosomal miR-130a-3p regulates osteogenic differentiation of Human Adipose-Derived stem cells through mediating SIRT7/Wnt/β-catenin axis.

It is of profound significance for clinical bone regeneration to clarify the specific molecular mechanism from which we found that osteogenic differentiation of adipose-derived stem cells (ADSCs) will be probably promoted by exosomes. By means of lentiviral transfection, miR-130a-3p overexpression and knockdown ADSCs were constructed. Alizarin Red S was used to detect the calcium deposits, and qPCR was used to detect osteogenesis-related genes, to verify the effect of miR-130a-3p on the osteogenic differentiation of ADSCs. CCK-8 was used to detect the effect of miR-130a-3p on the proliferation of ADSCs. The target binding between miR-130a-3p and SIRT7 was verified by dual-luciferase reporter gene assay. Furthermore, the role of Wnt signalling pathway in the regulation of ADSCs osteogenesis and differentiation by miR-130a-3p was further verified by detecting osteogenic-related genes and proteins and alkaline phosphatase activity. (a) Overexpression of miR-130a-3p can enhance the osteogenic differentiation of ADSCs while reducing protein and mRNA levels of SIRT7, a target of miR-130a-3p. (b) Our study further found that overexpression of miR-130a-3p leads to down-regulation of SIRT7 expression with up-regulation of Wnt signalling pathway-associated protein. (c) Overexpression of miR-130a-3p inhibited proliferation of ADSCs, while knockdown promoted it. The obtained findings indicate that exosomal miR-130a-3p can promote osteogenic differentiation of ADSCs partly by mediating SIRT7/Wnt/β-catenin axis, which will hence promote the application of exosomal microRNA in the field of bone regeneration.

Yang S ，Guo S ，Tong S ，Sun X ... -  《-》

MiR-486-3p promotes osteogenic differentiation of BMSC by targeting CTNNBIP1 and activating the Wnt/β-catenin pathway.

Dysfunction in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) leads to bone loss/osteoporosis. The catenin beta interacting protein 1 (CTNNBIP1) is an inhibitor of Wnt/β-catenin signaling, whose role in osteogenesis remains elusive. This study aimed to reveal the effects of miR-486-3p/CTNNBIP1 in osteogenesis. Bone marrow samples from healthy individuals and osteoporosis patients and mice with sham or ovariectomy (OVX) surgeries were collected. Levels of CTNNBIP1 and miR-486-3p were assessed. A dual-luciferase reporter assay was used to confirm the interactions between CTNNBIP1 and miR-486-3p. MiR-486-3p mimics/inhibitor or CTNNBIP1 overexpression lentiviruses were transfected to human BMSCs (hBMSCs) and an osteogenic assay was performed. Alizarin red S (ARS) and Alkaline phosphatase (ALP) intensity and expression of osteogenic genes Runx2, Alp, Cola1 and Bglap were measured. Key proteins in the Wnt/β-catenin pathway including active β-catenin, Bcl-2, and Cyclin D1 were assessed. CTNNBIP1 was upregulated while miR-486-3p was downregulated in osteoporosis patients and OVX mice. CTNNBIP1 was confirmed as a target of miR-486-3p. MiR-486-3p overexpression promoted, while miR-486-3p knockdown suppressed, osteogenic differentiation and Wnt/β-catenin signaling. Rescue experiments confirmed the negative effects of CTNNBIP1 overexpression on osteoblastic differentiation and that miR-486-3p mimics could reverse canonical Wnt signaling. This study demonstrated that miR-486-3p targets CTNNBIP1, thus activating the Wnt/β-catenin signaling pathway to promote osteogenesis of BMSCs.

Zhang Z ，Jiang W ，Hu M ，Gao R ，Zhou X ... -  《-》

MiR-122-3p regulates the osteogenic differentiation of mouse adipose-derived stem cells via Wnt/β catenin signaling pathway.

Hao W ，Liu HZ ，Zhou LG ，Sun YJ ，Su H ，Ni JQ ，He T ，Shi P ，Wang X ... -  《-》

The osteogenic differentiation of human adipose-derived stem cells is regulated through the let-7i-3p/LEF1/β-catenin axis under cyclic strain.

Luo Y ，Ge R ，Wu H ，Ding X ，Song H ，Ji H ，Li M ，Ma Y ，Li S ，Wang C ，Du H ... -  《Stem Cell Research & Therapy》

The lncRNA H19/miR-541-3p/Wnt/β-catenin axis plays a vital role in melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells.

Han H ，Tian T ，Huang G ，Li D ，Yang S ... -  《Aging-US》