Wnt/β-catenin signaling enhances osteoblastogenic differentiation from human periodontal ligament fibroblasts.
Wnt/β-catenin signaling has been known to influence bone formation and homeostasis. In this study, we investigated the canonical Wnt signaling regulation of osteogenic differentiation from periodontal ligament (PDL) fibroblasts. Stimulating PDL fibroblasts with lithium chloride (LiCl), a canonical Wnt activator, significantly increased mineralized nodule and alkaline phosphatase (ALP) activity in a time- and dose-dependent manner. LiCl up-regulated protein expression of osteogenic transcription factors, including the runt-related gene 2, Msx2, and Osterix 2, in the PDL fibroblasts. Treatment of these cells with LiCl also increased the mRNA levels of ALP, FosB, and Fra1 in a dose-dependent manner. Blockage of canonical Wnt signaling by treating the cells with DKK1 inhibited Wnt1-stimulated mRNA expression of these osteogenic factors. Furthermore, pretreatment with DKK1 reduced the ALP activity and matrix mineralization stimulated by Wnt1. Collectively, these results suggest that canonical Wnt signaling leads to the differentiation of PDL fibroblasts into osteogenic lineage with the attendant stimulation of osteogenic transcription factors.
Heo
Jung Sun
JS
Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Korea.
Lee
Seung-Youp
SY
Lee
Jeong-Chae
JC
D000328:Adult; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*; D000099169:Fos-Related Antigen 1
D000469:Alkaline Phosphatase; D036341:Intercellular Signaling Peptides and Proteins; D018021:Lithium Chloride; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D000099169:Fos-Related Antigen 1; C501126:DKK1 protein, human; C064269:FOSB protein, human