Splicing factor-modulated generation of mechano growth factor regulates physiological processes in osteoblasts under mechanical stimuli

Qian Yi; Huan Liu; Jianguo Feng; Yanjiao Wu; Weichao Sun; Mengting Ou; Liling Tang

doi:10.1080/19336918.2019.1686103

Splicing factor-modulated generation of mechano growth factor regulates physiological processes in osteoblasts under mechanical stimuli

Cell Adh Migr. 2019 Dec;13(1):322-331. doi: 10.1080/19336918.2019.1686103.

Authors

Qian Yi^{1

2}, Huan Liu³, Jianguo Feng⁴, Yanjiao Wu¹, Weichao Sun¹, Mengting Ou¹, Liling Tang¹

Affiliations

¹ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
² Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China.
³ Department of Orthopaedics, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
⁴ Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

Abstract

Mechanical stimuli influence various physiological processes in osteoblasts. We previously showed that mechano-growth factor (MGF), a splicing variant of insulin-like growth factor 1, is highly expressed in osteoblasts in response to mechanical stimuli. This study aims to explore the systemic functions of MGF in osteoblasts, and the mechanisms by which mechanical stress regulates the alternative splicing of Igf1 to generate MGF. We found that MGF promoted the proliferation and migration of osteoblasts, while it inhibited their differentiation via Erk1/2 pathway. Furthermore, cyclic stretching upregulated the expression of ASF/SF2, which in turn regulated the expression of MGF. Our findings indicate that mechanical stimuli influence the physiological responses of osteoblasts by increasing the expression of MGF, which is regulated by splicing factors.

Keywords: ASF/SF2 proteins; Erk1/2 signal pathway; MGF; Mechanical stimuli; osteoblasts.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing / genetics
Animals
Bone Remodeling / physiology
Cell Differentiation / genetics
Cell Movement / genetics
Cell Proliferation / genetics
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases / metabolism
Gene Expression Regulation / genetics
Insulin-Like Growth Factor I / genetics*
Insulin-Like Growth Factor I / metabolism*
Osteoblasts / cytology
Osteoblasts / physiology*
Protein Isoforms / genetics
Rats
Rats, Wistar
Serine-Arginine Splicing Factors / metabolism
Stress, Mechanical*

Substances

Protein Isoforms
insulin-like growth factor-1, rat
mechano-growth factor, mouse
Serine-Arginine Splicing Factors
Insulin-Like Growth Factor I
Extracellular Signal-Regulated MAP Kinases

Grants and funding

This study was sponsored by the National Natural Science Foundation of China (No31670952); The Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology (Chongqing University), the Ministry of Education (CQKLBST-2018-017, CQKLBST-2014-001); The Fundamental Research Funds for Central Universities (2018CDQYSG0021); and The Scientific Research Foundation of Southwest Medical University (2017-ZRZD-021).