Excessive BMP3b suppresses skeletal muscle differentiation

Shoichiro Kokabu; Nao Kodama; Aki Miyawaki; Kunikazu Tsuji; Jun Hino; Yusuke Ono; Takuma Matsubara

doi:10.1016/j.bbrc.2024.151261

Excessive BMP3b suppresses skeletal muscle differentiation

Biochem Biophys Res Commun. 2024 Dec 28:746:151261. doi: 10.1016/j.bbrc.2024.151261. Online ahead of print.

Authors

Shoichiro Kokabu¹, Nao Kodama², Aki Miyawaki², Kunikazu Tsuji³, Jun Hino⁴, Yusuke Ono⁵, Takuma Matsubara²

Affiliations

¹ Molecular Signaling and Biochemistry, Kyushu Dental University, Kokurakitaku, Kitakyushu, Fukuoka, Japan. Electronic address: r14kokabu@fa.kyu-dent.ac.jp.
² Molecular Signaling and Biochemistry, Kyushu Dental University, Kokurakitaku, Kitakyushu, Fukuoka, Japan.
³ Department of Orthopedic Surgery, Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan.
⁴ Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Japan.
⁵ Department of Muscle Development and Regeneration, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan; Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.

PMID: 39742789
DOI: 10.1016/j.bbrc.2024.151261

Abstract

Bone morphogenetic protein (BMP)-3b, also known as growth differentiation factor (GDF)-10, belongs to the transforming growth factor (TGF)-β superfamily. Despite being named a BMP, BMP3b is considered as an intermediate between the TGFβ/activin/myostatin and BMP/GDF subgroups of the TGFβ superfamily. Myoblast differentiation is tightly regulated by various cytokines, including the TGFβ superfamily members. However, despite BMP3b supporting the maintenance of skeletal myofibers, myoblast differentiation induced by BMP3b remains unclear. In this study, BMP3 expression levels in isolated satellites were very low compared to those in the skeletal muscle tissues. We analyzed cardiotoxin-induced muscle regeneration. Intact muscle fiber size was larger in BMP3b null mice than in wild-type mice; however, regenerated muscle fiber size did not differ between the null and wild-type mice. Next, we analyzed the satellite cell-specific BMP3b-overexpressing (BMP3b Tg) mice. Intact fiber size was increased in BMP3b Tg mice. However, regenerating tibialis anterior muscle size was reduced in BMP3b Tg mice compared to that in control mice. BMP3b overexpression in C2C12 cells stimulated Smad2/3 signaling. Moreover, BMP3b overexpression and conditioned medium of BMP3b-expressing Chinese hamster ovary cells strongly suppressed myoblast differentiation by repressing transactivation. Overall, our data suggest that BMP3b is not necessary for muscle regeneration; however, excessive BMP3b interferes with muscle regeneration by suppressing myoblast differentiation.

Keywords: Bone morphogenic protein; Differentiation; Regeneration; Skeletal muscle.