Baicalein Treatment Promotes Osteoblast Proliferation and Osteogenic Differentiation through Activation of Immediate Early Response 3
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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 and interleukin 1 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.
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 and interleukin 1 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.
참고문헌 (21)
- Bruce L Pihlstrom, "Periodontal diseases", The Lancet, 366(9499), pp.1809~1820 (2005), Elsevier BV[DOI]
- 이상임, "NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells", 치위생과학회지, 15(6), pp.753~760 (2015), 한국치위생과학회
- Lars A. Christersson, "Tissue Localization of Actinobacillus actinomycetemcomitans in Human Periodontitis", Journal of Periodontology, 58(8), pp.529~539 (1987), Wiley[DOI]
- G. Serino, "The effect of systemic antibiotics in the treatment of patients with recurrent periodontitis", Journal of Clinical Periodontology, 28(5), pp.411~418 (2001), Wiley[DOI]
- Forner L, "Increased plasma levels of IL-6 in bacteremic periodontis patients after scaling", J Clin Periodontol, 33, pp.724~729 (2006)[DOI]
- Bochra Kouidhi, "Drug resistance of bacterial dental biofilm and the potential use of natural compounds as alternative for prevention and treatment", Microbial Pathogenesis, 80, pp.39~49 (2015), Elsevier BV[DOI]
- Sang-Im Lee, "Role of SIRT1 in Heat Stress- and Lipopolysaccharide-induced Immune and Defense Gene Expression in Human Dental Pulp Cells", Journal of Endodontics, 37(11), pp.1525~1530 (2011), Elsevier BV[DOI]
- 이상임, "Protective Effects of Ursolic Acid on Osteoblastic Differentiation via Activation of IER3", Nrf2, 2019, pp.19(3), 198~204[DOI]
- Sang-Im Lee, "Baicalein Promotes Angiogenesis and Odontoblastic Differentiation via the BMP and Wnt Pathways in Human Dental Pulp Cells", The American Journal of Chinese Medicine, 44(07), pp.1457~1472 (2016), World Scientific Pub Co Pte Lt[DOI]
- Tim Mosmann, "Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays", Journal of Immunological Methods, 65(1-2), pp.55~63 (1983), Elsevier BV[DOI]
- Baruch Narotzki, "Green tea: A promising natural product in oral health", Archives of Oral Biology, 57(5), pp.429~435 (2012), Elsevier BV[DOI]
- Eun-Jin Jang, "Combination effects of baicalein with antibiotics against oral pathogens", Archives of Oral Biology, 59(11), pp.1233~1241 (2014), Elsevier BV[DOI]
- Xuan Li, "Nanoparticle-encapsulated baicalein markedly modulates pro-inflammatory response in gingival epithelial cells", Nanoscale, 9(35), pp.12897~12907 (2017), Royal Society of Chemistry (RSC)[DOI]
- Dai C, "Baicalein acts as a nephroprotectant that ameliorates colistin-induced nephrotoxicity by activating the antioxidant defence mechanism of the kidneys and down-regulating the inflammatory response", J Antimicrob Chemother, 72, pp.2562~2569 (2017)[DOI]
- Da-di Jin, "Regulation of bone formation by baicalein via the mTORC1 pathway", Drug Design, Development and Therapy, pp.5169~ (2015), Informa UK Limited[DOI]
- Lai CH, "Effects of 6-hydroxyflavone on osteoblast differentiation in MC3T3-E1cells", Evid Based Complement Alternat Med, pp.924560~ (2014)[DOI]
- Alexander Arlt, "Role of the immediate early response 3 (IER3) gene in cellular stress response, inflammation and tumorigenesis", European Journal of Cell Biology, 90(6-7), pp.545~552 (2011), Elsevier BV[DOI]
- Rajiv Kumar, "A Novel Immediate Early Response Gene, IEX-1, Is Induced by Ultraviolet Radiation in Human Keratinocytes", Biochemical and Biophysical Research Communications, 253(2), pp.336~341 (1998), Elsevier BV[DOI]
- Yu Wang, "Early proliferation alteration and differential gene expression in human periodontal ligament cells subjected to cyclic tensile stress", Archives of Oral Biology, 56(2), pp.177~186 (2011), Elsevier BV[DOI]
- Hanyong Jin, "IER3 is a crucial mediator of TAp73β-induced apoptosis in cervical cancer and confers etoposide sensitivity", Scientific Reports, 5(1) (2015), Springer Science and Business Media LLC[DOI]
- Jin Mi Kim, "Baicalein stimulates osteoblast differentiation via coordinating activation of MAP kinases and transcription factors", Journal of Cellular Biochemistry (2008), Wiley[DOI]