Osteogenic properties of human myogenic progenitor cells.
Here, we identified human myogenic progenitor cells coexpressing Pax7, a marker of muscle satellite cells and bone-specific alkaline phosphatase, a marker of osteoblasts, in regenerating muscle. To determine whether human myogenic progenitor cells are able to act as osteoprogenitor cells, we cultured both primary and immortalized progenitor cells derived from the healthy muscle of a nondystrophic woman. The undifferentiated myogenic progenitors spontaneously expressed two osteoblast-specific proteins, bone-specific alkaline phosphatase and Runx2, and were able to undergo terminal osteogenic differentiation without exposure to an exogenous inductive agent such as bone morphogenetic proteins. They also expressed the muscle lineage-specific proteins Pax7 and MyoD, and lost their osteogenic characteristics in association with terminal muscle differentiation. Both myoblastic and osteoblastic properties are thus simultaneously expressed in the human myogenic cell lineage prior to commitment to muscle differentiation. In addition, C3 transferase, a specific inhibitor of Rho GTPase, blocked myogenic but not osteogenic differentiation of human myogenic progenitor cells. These data suggest that human myogenic progenitor cells retain the capacity to act as osteoprogenitor cells that form ectopic bone spontaneously, and that Rho signaling is involved in a critical switch between myogenesis and osteogenesis in the human myogenic cell lineage.
Hashimoto
Naohiro
N
Stem Cell Research Team, Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. nao@nils.go.jp
Kiyono
Tohru
T
Wada
Michiko R
MR
Umeda
Rieko
R
Goto
Yu-ichi
Y
Nonaka
Ikuya
I
Shimizu
Shirabe
S
Yasumoto
Shigeru
S
Inagawa-Ogashiwa
Masayo
M
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D024510:Muscle Development / Q000502:physiology*; D017570:MyoD Protein / Q000032:analysis / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000032:analysis / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D017570:MyoD Protein; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; C493709:RUNX2 protein, human; D016212:Transforming Growth Factor beta; D020741:rho GTP-Binding Proteins