J Dent Hyg Sci.  2019 Dec;19(4):254-260. 10.17135/jdhs.2019.19.4.254.

Baicalein Treatment Promotes Osteoblast Proliferation and Osteogenic Differentiation through Activation of Immediate Early Response 3

• Lee SI

• KMID: 2469741
• DOI: http://doi.org/10.17135/jdhs.2019.19.4.254

Abstract

BACKGROUND
The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression.
METHODS
Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting.
RESULTS
Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2.
CONCLUSION
Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.

Keyword

Baicalein; Immediate early response 3 protein; Osteogenesis; Periodontal disease

MeSH Terms

Anti-Bacterial Agents
Anti-Inflammatory Agents
Biological Products
Blotting, Western
Calculi
Cell Proliferation
Cytokines
Dental Plaque
Down-Regulation
Humans
Inflammation
Interleukins
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Osteoblasts*
Osteogenesis
Periodontal Diseases
Periodontal Ligament
Phosphorylation
Phosphotransferases
Real-Time Polymerase Chain Reaction
Regeneration
RNA, Messenger
Signal Transduction
Tooth Loss
Transcription Factors
Tumor Necrosis Factor-alpha
Up-Regulation
Anti-Bacterial Agents
Anti-Inflammatory Agents
Biological Products
Cytokines
Interleukins
JNK Mitogen-Activated Protein Kinases
Phosphotransferases
RNA, Messenger
Transcription Factors
Tumor Necrosis Factor-alpha