A novel adipokine C1q/TNF-related protein 3 is expressed in developing skeletal muscle and controls myoblast proliferation and differentiation.
Several hormones and growth factors, including adipokines, play important roles during muscle development and regeneration. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 is a novel adipokine previously reported to reduce glucose output in hepatocytes and lower glucose levels in mice models. In the present study, we provide the first evidence for a physiological role of the CTRP3 in myogenesis using C2C12 myoblasts. CTRP3 was expressed in developing skeletal muscle tissues, and the expression level of CTRP3 was increased during myogenic differentiation of C2C12 cells. Recombinant CTRP3 (rCTRP3) promoted the proliferation of undifferentiated C2C12 myoblasts and this response required activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In contrary, rCTRP3 inhibited myogenic differentiation and fusion of C2C12 cells by suppressing the expression of myogenic marker genes (myogenin and myosin heavy chain). CTRP3 mRNA expression was increased in C2C12 myoblasts treated with transforming growth factor-β3 (TGF-β3), suggesting that TGF-β3 is one of the extracellular factors regulating CTRP3 expression during myogenesis. These results indicate a novel physiological role for CTRP3 during skeletal myogenesis.
Department of Anatomy and Cell Biology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.|Department of Dentistry and Oral Surgery, Yukioka Hospital, Osaka, Japan.
Masataka
M
Otani
Department of Radiology, Graduate School of Dentistry, Osaka University, Osaka, Japan.
Souhei
S
Furukawa
Department of Anatomy and Cell Biology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Satoshi
S
Wakisaka
Department of Anatomy and Cell Biology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan. tmaeda@dent.osaka-u.ac.jp.
Takashi
T
Maeda
D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism*; D018008:Myogenin / Q000096:biosynthesis; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology
D054392:Adipokines; C428135:CORS26 protein, mouse; D018008:Myogenin; D012333:RNA, Messenger; D053782:Transforming Growth Factor beta3; D048049:Extracellular Signal-Regulated MAP Kinases; D018995:Myosin Heavy Chains
C2C12 cells; CTRP3; ERK1/2; Myogenesis; TGF-β3