title: Involvement of p38MAPK/NF-κB signaling pathways in osteoblasts differentiation in response to mechanical stretch.
abstract: Bone morphogenetic proteins (BMPs) are known to be important in osteoblasts' response to mechanical stimuli. BMPs/Smad signaling pathway has been demonstrated to play a regulatory role in the mechanical signal transduction in osteoblasts. However, little is currently known about the Smad independent pathway in osteoblasts differentiation in mechanical loading. In this study, MC3T3-E1 cells were subjected to mechanical stretch of 2000 micro-stain (με) at 0.5 Hz, in order to investigate the involvement of p38MAPK and NF-κB signaling pathways in mechanical response in osteoblasts. We found BMP-2/BMP-4 were up-regulated by mechanical stretch via the earlier activation of p38MAPK and NF-κB signaling pathways, which enhanced osteogenic gene expressions including alkaline phosphatase (ALP), collagen type I (Col I) and osteocalcin (OCN), and the expressions of these osteogenic genes were remarkably decreased with Noggin (an inhibitor for BMPs signals) pretreatment. Furthermore, BMP-2/BMP-4 expressions were suppressed by PDTC, an inhibitor of NF-κB pathway and SB203580, an inhibitor of p38MAPK pathway, respectively, leading to the declined levels of ALP, Col I and OCN. Interestingly, blocking in p38MAPK pathway can also cause the inactivation of NF-κB pathway in mechanical stretch. Collectively, the results indicate during mechanical stretch p38MAPK and NF-κB signaling pathways are activated first, and then up-regulate BMP-2/BMP-4 to enhance osteogenic gene expressions. Moreover, p38MAPK and NF-κB signals have cross-talk in regulation of BMP-2/BMP-4 in mechanical response.
authors.affiliation: Tianjin Institute of Medical Equipment, No. 106 Wandong Road, Hedong District, Tianjin, 300161, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Jian-yu
authors.initials: JY
authors.lastname: Li
authors.forename: Xi-zheng
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Zong-ming
authors.initials: ZM
authors.lastname: Wan
authors.forename: Rui-xin
authors.initials: RX
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D024042:Collagen Type I; D016328:NF-kappa B; D012333:RNA, Messenger; D015675:Osteocalcin; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase