Extracellular Signal‐Regulated Kinase 1/2 Is Involved in Ascorbic Acid–Induced Osteoblastic Differentiation in Periodontal Ligament Cells

• Published in: Journal of periodontology (1970) 2007-02, Vol.78 (2), p.328-334
• Main Authors: Mimori, Kaori, Komaki, Motohiro, Iwasaki, Kengo, Ishikawa, Isao
• Format: Article
• Language: English
• Subjects: Adult; Alkaline phosphatase; Alkaline Phosphatase - biosynthesis; Alkaline Phosphatase - genetics; ascorbic acid; Ascorbic Acid - pharmacology; Biological and medical sciences; Blotting, Western; Cell Differentiation - drug effects; Cells, Cultured; collagen; Collagen Type I - physiology; Core Binding Factor Alpha 1 Subunit - biosynthesis; Core Binding Factor Alpha 1 Subunit - genetics; Dentistry; extracellular signal‐regulated kinase; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; Flavonoids - pharmacology; Humans; Integrins - physiology; Male; MAP Kinase Signaling System; Medical sciences; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - physiology; Non tumoral diseases; osteoblasts; Osteoblasts - cytology; Osteocalcin - biosynthesis; Osteocalcin - genetics; Otorhinolaryngology. Stomatology; periodontal ligament; Periodontal Ligament - cytology; Periodontal Ligament - enzymology; Polymerase Chain Reaction; Up-Regulation
• ISSN: 0022-3492; 1943-3670
• DOI: 10.1902/jop.2007.060223

Background: Periodontal ligament (PDL) cells possess osteoblast‐like properties and play key roles in periodontal regeneration. Previously, we have reported that ascorbic acid promotes the osteoblastic differentiation of PDL cells by modulating the type I collagen–integrin interaction. However, the signaling pathway activated following collagen–integrin interaction is still unclear. In this study, we examined the involvement of extracellular signal‐regulated kinase (ERK)1/2 in the expression of osteoblastic marker genes such as the osteoblast‐specific transcriptional factor runt‐related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteocalcin (OCN) in PDL cells. Methods: PDL cells were cultured on a conventional or type I collagen–coated dish in the presence or absence of ascorbic acid and examined for ALP activity and osteoblastic marker genes. For detection of ERK1/2, cells were plated on a petri (non‐adhesive) dish or type I collagen–coated dish, and Western blot analysis was performed. The effect of the ERK1/2 inhibitor on osteoblastic marker gene expression was examined. Results: Ascorbic acid increased gene expression of Runx2, ALP, and OCN. A combination of ascorbic acid and type I collagen remarkably upregulated Runx2, ALP, and OCN gene expression and ALP activity. Western blot analysis revealed an increased level of ERK1/2 phosphorylation in cells plated on type I collagen. An ERK1/2 inhibitor suppressed ascorbic acid–induced ALP and OCN gene expression, whereas Runx2 was not affected in PDL cells. Conclusion: These results indicate that ERK1/2 is involved in ascorbic acid–induced osteoblastic differentiation during PDL cell attachment to type I collagen.