MicroRNA‐203 promotes proliferation, differentiation, and migration of osteoblasts by upregulation of Msh homeobox 2. Issue 10 (10th March 2019)

• Record Type: Journal Article
• Authors: Liu, Haochuan; Chen, Bing; Li, Yi
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 10(2019:Oct.)
• Page Start: 17639
• Page End: 17648
• Publication Date: 2019-03-10
• Subjects: fracture healing -- mitogen‐activated protein kinase (MAPK)/activator of transcription (STAT) -- microRNA (miR)‐203 -- Msh homeobox 2 (Msx2) -- osteoblast; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28387
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Despite the improvements in fracture healing, about 10% of patients undergo abnormal healing. As a tumor suppressor, upregulation of microRNA (miR)‐203 has been observed in osteogenic differentiation. Herein, we aimed to explore the functional role of miR‐203 in osteoblasts as well as the underlying mechanisms. The expression of miR‐203 in MC3T3‐E1 cells that underwent osteogenic differentiation was determined by quantitative reverse transcription PCR (qRT‐PCR). The effects of aberrantly expressed miR‐203 on cell viability, migration, and expressions of proteins associated with proliferation, migration, and osteogenic differentiation were measured by using a Cell Counting Kit‐8 assay, Transwell cell migration assay, and western blot/qRT‐PCR, respectively. The possible downstream factor of miR‐203 was subsequently studied. Finally, involvements of the mitogen‐activated protein kinase (MAPK)/activator of transcription (STAT) pathways were assessed by western blot. We found that the miR‐203 level was increased in osteogenic differentiation of MC3T3‐E1 cells with increasing duration time (28th day, p < 0.001). After cell transfection, we interestingly found that miR‐203 overexpression could increase cell viability ( p < 0.05), promote proliferation, migration ( p < 0.05), and osteogenic differentiation, and upregulate Msh homeobox 2 (Msx2) expression. Furthermore, Msx2 knockdown was proved to abrogate the effects of miR‐203 overexpression on MC3T3‐E1 cells. Finally, phosphorylated levels of key kinases in the MAPK/STAT pathways were increased by miR‐203 overexpression via upregulating Msx2 expression. In conclusion, miR‐203 overexpression promoted proliferation, migration, and osteogenic differentiation of MC3T3‐E1 cells through upregulating Msx2 along with activation of the MAPK/STAT pathways. Abstract : microRNA (miR)‐203 overexpression promoted proliferation, migration, and osteogenic differentiation of MC3T3‐E1 cells through upregulating Msx2 along with the activation of the mitogen‐activated protein kinase (MAPK)/activator of transcription (STAT) pathways. Highlights: 1. miR‐203 is upregulated in osteogenic differentiation of MC3T3‐E1 cells; 2. miR‐203 promotes proliferation, migration, and osteogenic differentiation of MC3T3‐E1 cells; 3. miR‐203 affects MC3T3‐E1 cells via upregulating Msx2; 4. miR‐203 activates the MAPK/STAT pathways via upregulating Msx2.