Ultrasound increased BMP-2 expression via PI3K, Akt, c-Fos/c-Jun, and AP-1 pathways in cultured osteoblasts.
It has been shown that ultrasound (US) stimulation accelerates fracture healing in the animal models and in clinical studies. Bone morphogenetic protein (BMP) is a crucial mediator in bone formation during fracture healing. Here we found that US stimulation increased BMP-2 expression but not other BMPs. US induced BMP-2 transcription is mediated by AP-1 element but not estrogen receptor response element and GC-rich Sp1 response element. Pretreatment of osteoblasts with phosphatidylinositol 3-kinase (PI3K) inhibitor (Ly294002) and Akt inhibitor inhibited the potentiating action of US; these results were further substantiated by transfecting with the dominant negative mutants of p85 and Akt. US stimulation increased the phosphorylation of p85 subunit of PI3K and serine 473 of Akt. Transfection of osteoblasts with c-Fos and c-Jun antisense oligonucleotide also reduced US-increased BMP-2 expression. US-increased the binding of c-Fos and c-Jun to the AP-1 element on the BMP-2 promoter and the enhancement of AP-1 luciferase activity was inhibited by Ly294002 and Akt inhibitor. Our results suggest that US increased BMP-2 expression in osteoblasts via the PI3K, Akt, c-Fos/c-Jun, and AP-1 signaling pathway.
Hou
Chun-Han
CH
Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
Hou
Sheng-Mou
SM
Tang
Chih-Hsin
CH
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014465:Ultrasonics
D055396:Bone Morphogenetic Protein 2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt