title: Expression of Caveolin-1 in Periodontal Tissue and Its Role in Osteoblastic and Cementoblastic Differentiation In Vitro.
abstract: It has been previously reported that caveolin-1 (Cav-1) knockout mice exhibit increased bone size and stiffness. However, the expression and role of Cav-1 on periodontal tissue is poorly understood. The aim of this study was to investigate the immunohistochemical expression of Cav-1 in the mouse periodontium and explore the role of Cav-1 on osteoblastic and cementoblastic differentiation in human periodontal ligament cells (hPDLCs), cementoblasts, and osteoblasts. To reveal the molecular mechanisms of Cav-1 activity, associated signaling pathways were also examined. Immunolocalization of Cav-1 was studied in mice periodontal tissue. Differentiation was evaluated by ALP activity, alizarin red S staining, and RT-PCR for marker genes. Signal transduction was analyzed using Western blotting and confocal microscopy. Cav-1 expression was observed in hPDLCs, cementoblasts, and osteoblasts of the periodontium both in vivo and in vitro. Inhibition of Cav-1 expression by methyl-β-cyclodextrin (MβCD) and knockdown of Cav-1 by siRNA promoted osteoblastic and cementoblastic differentiation by increasing ALP activity, calcium nodule formation, and mRNA expression of differentiation markers in hPDLCs, cementoblasts, and osteoblasts. Osteogenic medium-induced BMP-2 and BMP-7 expression, and phosphorylation of Smad1/5/8 were enhanced by MβCD and siRNA knockdown of Cav-1, which was reversed by BMP inhibitor noggin. MβCD and Cav-1 siRNA knockdown increased OM-induced AMPK, Akt, GSK3β, and CREB phosphorylation, which were reversed by Ara-A, a specific AMPK inhibitor. Moreover, OM-induced activation of p38, ERK, JNK, and NF-κB was enhanced by Cav-1 inhibition. This study demonstrates, for the first time, that Cav-1 is expressed in developing periodontal tissue and in vitro in periodontal-related cells. Cav-1 inhibition positively regulates osteoblastic differentiation in hPDLCs, cementoblasts, and osteoblasts via BMP, AMPK, MAPK, and NF-κB pathway. Thus, Cav-1 inhibition may be a novel molecular target for therapeutic approaches in periodontitis or osteolytic disease.
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, 14 Kyungheedae-ro Dongdaemun-gu, Seoul, 02453, Republic of Korea.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Conservative Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Yi
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, 14 Kyungheedae-ro Dongdaemun-gu, Seoul, 02453, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Cheol-Hyeon
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Eui-Sic
authors.initials: ES
authors.lastname: Cho
authors.affiliation: Division of Dentistry, Department of Oral and Maxillofacial Radiology, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kook-Sun
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, 14 Kyungheedae-ro Dongdaemun-gu, Seoul, 02453, Republic of Korea. eckim@khu.ac.kr.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051242:Caveolin 1 / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003739:Dental Cementum / Q000166:cytology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000166:cytology*; D010513:Periodontal Ligament / Q000166:cytology / Q000254:growth & development; D010519:Periodontium / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051242:Caveolin 1
keywords: Caveolin-1; Differentiation; Expression; Periodontal ligament cells; Periodontium