Baicalein이 골수유래대식세포의 파골세포 분화에 미치는 효과
The Effects of Baicalein on Osteoclast Differentiation from Bone Marrow Derived Macrophage
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
현대사회가 급속한 노령화 시대에 접어들면서 뼈 건강에 대한 중요성이 증가됨으로써 최근, 천연물을이용한 골질환의 치료제를 개발하기 위한 연구가 활발히 이루어지고 있다. Baicalein은 기존에 항암, 항염증, 항산화의 효과가 있고, MC3T3-E1 조골세포주의 분화를 촉진하며, RAW264.7세포주의 분화는 억제한다는 보고가있다. 그러나 골수유래대식세포를 이용한 파골세포 분화의 억제기전에 대해서는 정확히 알려진 바가 없다. 그리하여 본 연구에서는 골수유래대식세포의 파골세포 분화에 있어 baicalein의 억제기전을 밝히고, 골수기질세포의조골세포 분화에 미치는 영향을 탐색하기 위한 실험을 진행하였다. 파골세포 분화를 위해 골수유래대식세포를 사용하여 분화, mRNA 및 단백질 발현을 확인하였다. 조골세포 분화를 위해 골수기질세포를 사용하여 분화, ALP활성 및 미네랄 침착능을 확인하였다. Baicalein은 골수유래대식세포에서 RANKL로 유도한 파골세포로의 분화를 세포독성 없이 농도 의존적으로억제하였다. 억제기전으로는 Akt, JNK, PLCγ2의 인산화를 억제하였고, NF-κB의 활성화를 억제하여 파골세포분화의 필수 유전자인 c-Fos 및 NFATc1의 발현 역시 억제하였다. 또한 TRAP, OSCAR, cathepsin K와 DCSTAMP의mRNA 수준의 발현을 감소시켰다. 이와 더불어, baicalein이 골 형성의 기능을 갖는 조골세포의 분화를 촉진하는 효과를 골수기질세포에서 확인하였다. Baicalein은 골수유래대식세포에서 파골세포 분화를 억제하고, 동시에 골수기질세포를 이용한 조골세포 분화를 높이는 양면적인 효과를 가지는 물질로, 향후 골 소실 질환 치료제 개발에 중요 후보물질이 될 것으로 사료된다.
Abstract
As prediction of rapidly aging society, bone health is considered increasingly important and receivedmore attention than ever. Bone health is regulated by balancing between bone resorptive osteoclasts and boneformative osteoblasts. Disruption of balance between bone-resorbing osteoclasts and bone-forming osteoblastsresults in bone disease. Natural products have recently received much attention as an alternative tool for thedevelopment of novel therapeutic strategy. Baicalein is reported it has anti-cancer, anti-inflammatory andantioxidant effects. Baicalein also has been known that it has both promotive effect on MC3T3-E1 cell line andinhibitory effect on RAW 264.7 cell line. However, the inhibitory mechanism of baicalein using bone marrowderived macrophages (BMMs) on osteoclast differentiation remains not clear. In this study, the suppressivemechanism by baicalein on osteoblast differentiation was evaluated. Bicalein inhibited receptor activator ofnuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in BMMs in a dose dependent mannerwithout any toxicity. Baicalein suppressed phosphorylation of protein kinaseB (Akt), c-Jun N-terminal kinases(JNK) and phosphoinositide-specific phospholipaseCγ2 (PLCγ2). Furthermore, Baicalein suppressed theinduction of RANKL-induced c-Fos and Nuclear factor of activated T cell c1 (NFATc1), essential genes onosteoclastogenesis. In BMMs, Bicalein inhibited the mRNA expression of tartrate-resistant acid phosphatase(TRAP), osteoclast-associated receptor (OSCAR), cathepsinK, dendritic cell-specific transmembrane protein (DCSTAMP). Moreover, baicalein promoted differentiation of osteoblast on bone marrow stromal cells (BMSCs). Taken together, these results suggest that baicalein has a potential for treating bone lytic diseases, such asosteoporosis, periodontitis, and rheumatoid arthritis.
참고문헌 (20)
- Gass M, "Preventing osteoporosis-related fractures: an overview", Am J Med, 119, pp.S3~S11 (2006)
- Raggatt LJ, "Cellular and molecular mechanisms of bone remodeling", J Biol Chem, 285, pp.25103~25108 (2010)
- Tanaka Y, "Osteoblasts and osteoclasts in bone remodeling and inflammation", Curr Drug Targets Inflamm Allergy, 4, pp.325~328 (2005)
- Roodman GD, "Regulation of Osteoclast Differentiation", Ann N Y Acad Sci, 1068, pp.100~109 (2006)
- Sakae T, "Signal transduction pathway regulating osteoclast differentiation and function", J Bone Miner Metab, 21, pp.123~133 (2003)
- Dickson KM, "TRAF6-Dependent NF-κB Transcriptional Activity During Mouse Development", Dev Dyn, 231, pp.122~127 (2004)
- Qing Hong Z, "The effect of rotative stress on CAII, FAS, FASL, OSCAR, and TRAP gene expression in osteoclasts", J Cell Biochem, 114, pp.388~397 (2013)
- Chao JI, "Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogenactivated protein kinase and AKT", Mol Cancer Ther, 6, pp.3039~3048 (2007)
- Lin CC, "The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin", Am J Chin Med, 24, pp.31~36 (1996)
- Lapchak PA, "Baicalein, an antioxidant 12", 15-lipoxygenase inhibitor improves clinical rating scores following multiple infarct embolic strokes, 2007, pp.150, 585~591
- Kuntz S, "Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines", Eur J Nutr, 38, pp.133~142 (1999)
- Kim MH, "Baicalein inhibits osteoclast differentiation and induces mature osteoclast apoptosis", Food Chem Toxicol, 46, pp.3375~3382 (2008)
- Kim JM, "Baicalein stimulates osteoblast differentiation via coordinating activation of MAP kinases and transcription factors", J Cell Biochem, 104, pp.1906~1917 (2007)
- Kennel KA, "Adverse effects of bisphosphonates:implications for osteoporosis management", Mayo Clin Proc, 84, pp.632~637 (2009)
- McClung M, "Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday", Am J Med, 126, pp.13~20 (2013)
- Li FQ, "Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons", J Neural Transm, 112, pp.331~347 (2005)
- Sultan KR, "Species-specific primary cell cultures: a research tool in veterinary science", Veterinary Sciences Tommorow, 1, pp.1~7 (2001)
- Kartsogiannis V, "Cell lines and primary cell cultures in the study of bone cell biology", Mol Cell Endocrinol, 228, pp.79~102 (2004)
- Burton NM, "Methods for animal satellite cell culture under a variety of conditions", Methods Cell Sci, 22, pp.51~61 (2000)
- Mao D, "PLCgamma2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2", J Clin Invest, 116, pp.2869~2879 (2006)