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BMP10 positively regulates myogenic differentiation in C2C12 myoblasts via the Smad 1/5/8 signaling pathway

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Abstract

BMP10 plays an essential role in regulating cardiac growth, chamber maturation, and maintaining normal expressions of several key cardiogenic factors; however, other functional roles of BMP10 in muscle remain unexplored. This study therefore undertook to investigate the roles of BMP10 in muscle physiology, using mouse-derived C2C12 myoblasts. Bmp10 silencing prevented a number of biological processes such as myogenic differentiation, glucose uptake, and lipid catabolism, whereas exogenous induction of BMP10 in C2C12 cells significantly stimulated the expression of proteins and genes involved in these processes, as well as mitochondrial biogenesis and thermogenesis, resulting in reduced lipid accumulation. A mechanistic study revealed that BMP10 stimulates myogenesis mainly via the Smad 1/5/8 signaling pathway. In conclusion, our data unveiled a previously unknown mechanism in the regulation of lipid metabolisms by BMP10 in muscle cells and identified its significant roles in systemic metabolic homeostasis, shedding light on BMP10 as a pharmacotherapeutic target to treat metabolic disorders.

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Abbreviations

ABHD5/Abhd5 :

1-acylglycerol-3-phosphate O-acyltransferase ABHD5 encoding gene

ACOX1:

acyl-coenzyme A oxidase 1

Actr2a :

activin receptor type-2a encoding gene

Actr2b :

activin receptor type-2b encoding gene

Acvr1 :

activin A receptor type 1 encoding gene

Acvrl1 :

activin receptor-like kinase 1 encoding gene

AKT/PKB:

protein kinase B

ATGL:

adipose triglyceride lipase

BMP10/Bmp10 :

bone morphogenetic protein 10/encoding gene

Bmpr1a :

bone morphogenetic protein receptor type IA encoding gene

Bmpr1b :

bone morphogenetic protein receptor type IB encoding gene

BMPR2/Bmpr2 :

bone morphogenetic protein receptor type II/encoding gene

BSA:

bovine serum albumin

CD36/Cd36 :

cluster of differentiation 36/encoding gene

COX4:

cytochrome c oxidase subunit 4

CPT1:

carnitine palmitoyltransferase 1

CYT-C:

cytochrome complex

FAS:

fatty acid synthase

Fatp1 :

long-chain fatty acid transport protein 1 encoding gene

FATP4/Fatp4 :

long-chain fatty acid transport protein 4/encoding gene

GDFs:

growth and differentiation factors

GLUT4:

glucose transporter type 4

HSL:

hormone-sensitive lipase

MYF5:

myogenic factor 5

MYH/Myh :

myosin heavy chain/encoding gene

MYOD:

myoblast determination protein 1

MYOG/Myog :

myogenin/encoding gene

Nrf1 :

nuclear respiratory factor 1 encoding gene

PGC-1α:

peroxisome proliferator-activated receptor gamma co-activator 1-alpha

Plin :

perilipin encoding gene

Ryr1 :

ryanodine receptor 1 encoding gene

SERCA2:

sarcoplasmic/endoplasmic reticulum calcium ATPase 2

Sln :

sarcolipin encoding gene

UCP/Ucp :

uncoupling protein/encoding gene

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Acknowledgements

This work was supported by a National Research Foundation of Korea grant funded by the Korean government (MSIT) (No. 2019R1A2C2002163).

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  1. Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk, 38453, Republic of Korea

    Trang Thi Huyen Dang & Jong Won Yun

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  1. Trang Thi Huyen Dang
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Correspondence to Jong Won Yun.

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Dang, T.T., Yun, J.W. BMP10 positively regulates myogenic differentiation in C2C12 myoblasts via the Smad 1/5/8 signaling pathway. Mol Cell Biochem 476, 2085–2097 (2021). https://doi.org/10.1007/s11010-021-04064-x

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