Journal Article

Focal Adhesion Kinase Signaling Mediated the Enhancement of Osteogenesis of Human Mesenchymal Stem Cells Induced by Extracorporeal Shockwave

Zhang, Yuantao, Hu, Jun, Liao, Haojie, Huang, Zhonglian, Chen, Hongjiang, Ma, Zebin, Yu, Menglei, Xu, Jiankun, Chen, Youbin

2016

Overview

Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs) and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate the underlying mechanisms. We show here that ESW (0.16 mj/mm 2 ) significantly promoted the osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of miR-138, but the activation of FAK, ERK1/2 and RUNX2. The enhancement of osteogenesis in these MSCs was consistently abolished when the cells were pretreated with one of the following conditions: overexpression of miR-138, FAK knockdown using specific siRNA and U0126, implying that all of these elements are indispensable for mediating the effect of ESW. Moreover, our study provides converging genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally activated in ESW-preconditioned MSCs, suggesting that ESW may be a promising therapeutic strategy for the enhancement of osteogenesis of MSCs, regardless of their origins.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/1 / 13/89 / 42 / 42/100 / 631/532/1360 / 639/766/747 / 82 / 82/80 / Adipose Tissue - cytology / Adipose Tissue - metabolism / Adipose Tissue - radiation effects / Adult / Animals / Antigens, CD - genetics / Antigens, CD - metabolism / Bone marrow / Bone Marrow Cells - cytology / Bone Marrow Cells - metabolism / Bone Marrow Cells - radiation effects / Butadienes - pharmacology / Cbfa-1 protein / Cell Differentiation - radiation effects / Core Binding Factor Alpha 1 Subunit - genetics / Core Binding Factor Alpha 1 Subunit - metabolism / Extracellular signal-regulated kinase / Focal adhesion kinase / Focal Adhesion Kinase 1 - genetics / Focal Adhesion Kinase 1 - metabolism / Gene Expression Regulation / High-Energy Shock Waves - therapeutic use / Humanities and Social Sciences / Humans / Male / Mesenchymal stem cells / Mesenchymal Stromal Cells - cytology / Mesenchymal Stromal Cells - metabolism / Mesenchymal Stromal Cells - radiation effects / Mesenchyme / Mice / Mice, Nude / MicroRNAs - genetics / MicroRNAs - metabolism / Mitogen-Activated Protein Kinase 1 - genetics / Mitogen-Activated Protein Kinase 1 - metabolism / Mitogen-Activated Protein Kinase 3 - genetics / Mitogen-Activated Protein Kinase 3 - metabolism / multidisciplinary / Nitriles - pharmacology / Osteogenesis / Osteogenesis - genetics / Osteogenesis - radiation effects / Primary Cell Culture / RNA, Small Interfering - genetics / RNA, Small Interfering - metabolism / Science / Shock waves / Signal Transduction / siRNA / Skin & tissue grafts / Stem cells / Tendons - cytology / Tendons - metabolism / Tendons - radiation effects