Ultrasound enhances transforming growth factor beta-mediated chondrocyte differentiation of human mesenchymal stem cells.
In clinical studies and animal models, low-intensity ultrasound (US) promotes fracture repair and increases mechanical strength. US also promotes cartilage healing by increasing glycosaminoglycan synthesis of chondrocytes. As mesenchymal stem cells (MSCs) have the ability to differentiate into chondrocytes, US may promote their differentiation. Here, we evaluated the effects of US on the differentiation of MSCs toward chondrocytes and cartilage matrix formation. When human MSCs cultured in pellets were treated with transforming growth factor beta (TGF-beta, 10 ng/mL), they differentiated into chondrocytes as assessed by alcian blue staining and immunostaining for aggrecan, but nontreated cell pellets did not. Furthermore, when low-intensity US was applied for 20 min every day to the TGF-beta-treated cell pellets, chondrocyte differentiation was enhanced. Biochemically, aggrecan deposition was increased by 2.9- and 8.7-fold by treatment with TGF-beta alone, and with both TGF-beta and US, respectively. In contrast, cell proliferation and total protein amount appeared unaffected by these treatments. These results indicate that low-intensity US enhances TGF-beta-mediated chondrocyte differentiation of MSCs in pellet culture and that application of US may facilitate larger preparations of chondrocytes and the formation of mature cartilage tissue.
Ebisawa
Katsumi
K
Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Hata
Ken-Ichiro
K
Okada
Kunihiko
K
Kimata
Koji
K
Ueda
Minoru
M
Torii
Shuhei
S
Watanabe
Hideto
H
D002356:Cartilage / Q000187:drug effects / Q000254:growth & development / Q000502:physiology / Q000528:radiation effects; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D011829:Radiation Dosage; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014465:Ultrasonics
D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta