Induction of myogenic differentiation by SDF-1 via CXCR4 and CXCR7 receptors.
The stromal cell-derived factor (SDF)-1/CXC receptor 4 (CXCR4) axis has been shown to play a role in skeletal muscle development, but its contribution to postnatal myogenesis and the role of the alternate SDF-1 receptor, CXC receptor 7 (CXCR7), are poorly characterized. Western blot analysis and real-time polymerase chain reaction (PCR) were performed to evaluate in vitro the effect of SDF-1 and CXCR4 and CXCR7 inhibition on myogenic differentiation. Proliferating myoblasts express CXCR4, CXCR7, and SDF-1; during myogenic differentiation, CXCR4 and CXCR7 levels are downregulated, and SDF-1 release is decreased. SDF-1 anticipates myosin heavy chain accumulation and myotube formation in both C2C12 myoblasts and satellite cells. Interestingly, inhibition of CXCR4 and CXCR7 signaling, either by drugs or RNA interfererence, blocks myogenic differentiation. Further, the CXCR4 antagonist, 4F-benzoyl-TN14003, inhibits myoblast cell cycle withdrawal and decreases the retinoblastoma gene (pRb) product accumulation in its hypophosphorylated form. Our experiments demonstrate that SDF-1 regulates myogenic differentiation via both CXCR4 and CXCR7 chemokine receptors.
Melchionna
Roberta
R
Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Via Monti di Creta 104, Rome 00167, Italy.
Di Carlo
Anna
A
De Mori
Roberta
R
Cappuzzello
Claudia
C
Barberi
Laura
L
Musarò
Antonio
A
Cencioni
Chiara
C
Fujii
Nobutaka
N
Tamamura
Hirokazu
H
Crescenzi
Marco
M
Capogrossi
Maurizio C
MC
Napolitano
Monica
M
Germani
Antonia
A
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000494:pharmacology; D005434:Flow Cytometry; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D054387:Receptors, CXCR / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics*
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C501897:Cmkor1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; D019718:Receptors, CXCR4