Baicalein Promotes Angiogenesis and Odontoblastic Differentiation via the BMP and Wnt Pathways in Human Dental Pulp Cells

Am J Chin Med. 2016;44(7):1457-1472. doi: 10.1142/S0192415X16500816. Epub 2016 Oct 25.

Abstract

Baicalein is an active flavonoid extracted from the root of Scutellaria baicalensis that has anticancer and anti-inflammatory properties; its effects on osteoblastic and angiogenic potential are controversial. The aim of this study was to investigate the effects of baicalein on odontoblastic differentiation and angiogenesis and the underlying mechanism in human dental pulp cells (HDPCs). Baicalein (1-10[Formula: see text][Formula: see text]M) had no cytotoxic effects and promoted alkaline phosphatase (ALP) activity, mineralization assayed by Alizarin Red-S staining, and the mRNA expression of marker genes, in a concentration-dependent manner. In addition, baicalein upregulated angiogenic factors and increased in vitro capillary-like tube formation. Moreover, baicalein upregulated bone morphogenetic protein (BMP)-2 mRNA and phosphorylation of Smad 1/5/8 and Wnt ligand mRNA, glycogen synthase kinase-3, and nuclear [Formula: see text]-catenin. The odontogenic and angiogenic effects of baicalein were abolished by the BMP antagonist noggin and the Wnt/[Formula: see text]-catenin receptor antagonist DKK-1. These results demonstrate that baicalein promoted odontoblastic differentiation and angiogenesis of HDPCs by activating the BMP and Wnt/[Formula: see text]-catenin signal pathways. Our findings suggest that baicalein may contribute to dental pulp repair and regenerative endodontics.

Keywords: Angiogenesis; BMP Pathway; Baicalein; Differentiation; Human Dental Pulp Cells; Wnt Pathway.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Angiogenesis Inducing Agents*
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Dental Pulp / cytology*
  • Dental Pulp / physiology
  • Dose-Response Relationship, Drug
  • Flavanones / isolation & purification
  • Flavanones / pharmacology*
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics*
  • Odontoblasts / cytology*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Regeneration / drug effects
  • Regeneration / physiology
  • Scutellaria baicalensis / chemistry*
  • Up-Regulation / drug effects
  • Wnt Signaling Pathway / drug effects*
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / physiology*

Substances

  • Angiogenesis Inducing Agents
  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Flavanones
  • Plant Extracts
  • Scutellaria baicalensis extract
  • beta Catenin
  • baicalein
  • Alkaline Phosphatase