title: Hydrostatic pressures promote initial osteodifferentiation with ERK1/2 not p38 MAPK signaling involved.
abstract: Mechanical stress has been considered to be an important factor in bone remodeling and recent publications have shown that mechanical stress can regulate the direction of stem cell differentiation. The exact mechanobiological effects of pressure on initial osteodifferentiation of mesenchymal stem cells (MSCs) have not been determined. These mechanobiological mechanisms may be important both in biological responses during orthodontic tooth movement and in the development of new mechanobiological strategies for bone tissue engineering. We investigated the effects of static (23 kPa) or dynamic (10-36 kPa and at 0.25 Hz frequency) pressure on MSCs during the initial process of osteoblastic differentiation following treatment with dexamethasone, beta-glycerophosphate and ascorbic acid (for 0, 3, and 7 days, respectively). The following parameters were analyzed in the ALPase activity, mRNA level of osteogenesis-related transcription factors (Runx2, Osterix, Msx2, and Dlx5), and phosphorylation of ERK1/2 and p38 MAPK. The results showed that exposure to either dynamic or static pressure induced initial osteodifferentiation of MSCs. Particularly both types of pressure strongly stimulated the expression of osteogenesis-related factors of totally undifferentiated MSCs. ERK signaling participated in early osteodifferentiation and played a positive but non-critical role in mechanotransduction, whereas p38 MAPK was not involved in this process. Furthermore, the undifferentiated MSCs were highly sensitive to pressure exposure; whereas after osteoinduction MSCs reacted to pressure in a lower response state. The findings should lead to further studies to unveil the complex initial biological mechanisms of bone remodeling and regeneration upon mechanical stimuli.
authors.affiliation: West China College of Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Zou
authors.forename: Charles
authors.initials: C
authors.lastname: Shuler
authors.forename: Yuanwen
authors.initials: Y
authors.lastname: Zou
authors.forename: Xuejin
authors.initials: X
authors.lastname: Huang
authors.forename: Mingli
authors.initials: M
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D016723:Bone Remodeling / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D006874:Hydrostatic Pressure; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; D014157:Transcription Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase