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Low-Intensity Pulsed Ultrasound Promotes BMP9 Induced Osteoblastic Differentiation in Rat Dedifferentiated Fat Cells
International Journal of Stem Cells
Published online June 30, 2023;  
© 2023 Korean Society for Stem Cell Research.

Fumiaki Setoguchi1, Kotaro Sena1,2, Kazuyuki Noguchi1

1Department of Periodontology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
2Division of Preventive Dentistry, Department of Community Social Dentistry, Graduate School of Dentistry, Tohoku University, Miyagi, Japan
Correspondence to: Kotaro Sena
Division of Preventive Dentistry, Department of Community Social Dentistry, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai-city, Miyagi 980-8575, Japan
Tel: +81-22-717-8327, Fax: +81-22-717-8325
Received March 11, 2023; Revised May 24, 2023; Accepted May 25, 2023.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background and Objectives: Dedifferentiated fat cells (DFATs) isolated from mature adipocytes have a multilineage differentiation capacity similar to mesenchymal stem cells and are considered as promising source of cells for tissue engineering. Bone morphogenetic protein 9 (BMP9) and low-intensity pulsed ultrasound (LIPUS) have been reported to stimulate bone formation both in vitro and in vivo. However, the combined effect of BMP9 and LIPUS on osteoblastic differentiation of DFATs has not been studied.
Methods and Results: After preparing DFATs from mature adipose tissue from rats, DFATs were treated with different doses of BMP9 and/or LIPUS. The effects on osteoblastic differentiation were assessed by changes in alkaline phosphatase (ALP) activity, mineralization/calcium deposition, and expression of bone related genes; Runx2, osterix, osteopontin. No significant differences for ALP activity, mineralization deposition, as well as expression for bone related genes were observed by LIPUS treatment alone while treatment with BMP9 induced osteoblastic differentiation of DFATs in a dose dependent manner. Further, co-treatment with BMP9 and LIPUS significantly increased osteoblastic differentiation of DFATs compared to those treated with BMP9 alone. In addition, upregulation for BMP9-receptor genes was observed by LIPUS treatment. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the synergistic effect of BMP9 and LIPUS co-stimulation on osteoblastic differentiation of DFATs.
Conclusions: LIPUS promotes BMP9 induced osteoblastic differentiation of DFATs in vitro and prostaglandins may be involved in this mechanism.
Keywords : Dedifferentiated fat cells, Bone morphogenetic protein 9, Low-intensity pulsed ultrasound, Prostaglandins

August 2023, 16 (3)
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