Fluid Shear Stress Stimulates Osteogenic Differentiation of Human Periodontal Ligament Cells via the Extracellular Signal‐Regulated Kinase 1/2 and p38 Mitogen‐Activated Protein Kinase Signaling Pathways

• Published in: Journal of periodontology (1970) 2014-12, Vol.85 (12), p.1806-1813
• Main Authors: Tang, Min, Peng, Zhuli, Mai, Zhihui, Chen, Lin, Mao, Qin, Chen, Zheng, Chen, Qi, Liu, Limin, Wang, Yuxuan, Ai, Hong
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - ultrastructure; Adolescent; Adult; Alkaline Phosphatase - analysis; Alkaline Phosphatase - drug effects; Biomechanical Phenomena; Butadienes - pharmacology; Calcification, Physiologic - drug effects; Calcification, Physiologic - physiology; Calcium - metabolism; Cell differentiation; Cell Differentiation - physiology; Cell Shape; Cell Survival - physiology; Cells, Cultured; Child; Collagen Type I - analysis; Dentistry; Female; Humans; Hydrodynamics; Imidazoles - pharmacology; Male; MAP Kinase Signaling System - physiology; Mitogen-Activated Protein Kinase 1 - analysis; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - physiology; Mitogen-Activated Protein Kinase 3 - analysis; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - physiology; Nitriles - pharmacology; Osteogenesis - genetics; Osteogenesis - physiology; p38 Mitogen-Activated Protein Kinases - analysis; p38 Mitogen-Activated Protein Kinases - physiology; p38 mitogen‐activated protein kinases; periodontal ligament; Periodontal Ligament - cytology; Periodontal Ligament - enzymology; Pyridines - pharmacology; Stress, Mechanical; Young Adult
• ISSN: 0022-3492; 1943-3670
• DOI: 10.1902/jop.2014.140244

Background: Fluid shear stress (FSS) is a major type of mechanical stress that is loaded on human periodontal ligament cells (hPDLCs) during mastication and orthodontic tooth movement. This study aims to clarify the effect of FSS on the osteogenic differentiation of hPDLCs and to further verify the involvement of mitogen‐activated protein kinase (MAPK) signaling in this process. Methods: After isolation and characterization, hPDLCs were subjected to 2‐hour FSS at 12 dynes/cm2, and cell viability, osteogenic gene mRNA expression, alkaline phosphatase (ALP) activity, secretion of Type I collagen (COL‐I), and calcium deposition were assayed. The levels of phosphorylated p38 and phosphorylated extracellular signal‐regulated kinase 1/2 (ERK1/2) in response to FSS were detected by Western blot, and the involvement of ERK1/2 and p38 MAPK signaling pathways in hPDLC osteogenesis under FSS was investigated using the specific MAPK inhibitors U0126 (2Z,3Z)‐2,3‐bis[amino(2‐aminophenylthio)methylene]succinonitrile,ethanol) and SB203580 (4‐[4‐(4‐fluorophenyl)‐2‐(4‐[methylsulfinyl]phenyl)‐1H‐imidazol‐5‐yl]pyridine). Results: The application of FSS on hPDLCs induced an early morphologic change and rearrangement of filamentous actin. ALP activity, messenger RNA (mRNA) levels of osteogenic genes, COL‐I, and osteoid nodules were significantly increased by FSS. Moreover, ERK1/2 and p38 were activated in different ways after FSS exposure. U0126 and SB203580 completely blocked the FSS‐induced increases in ALP activity and osteogenic gene mRNA expression and osteoid nodules formation. Conclusions: FSS is an effective approach for stimulating osteogenic differentiation of hPDLCs. The ERK1/2 and p38 MAPK signaling pathways are involved in this cellular process.