[논문]2-O-digalloyl-1,3,4,6-tetra-O-galloyl-β-D-glucose isolated from Galla Rhois suppresses osteoclast differentiation and function by inhibiting NF-κB signaling

Ihn, Hye Jung; Kim, Tae Hoon; Kim, Kiryeong; Kim, Gi-Young; Jeon, You-Jin; Choi, Yung Hyun; Bae, Jong-Sup; Kim, Jung-Eun; Park, Eui Kyun

doi:10.5483/bmbrep.2019.52.6.063

2-O-digalloyl-1,3,4,6-tetra-O-galloyl-β-D-glucose isolated from Galla Rhois suppresses osteoclast differentiation and function by inhibiting NF-κB signaling 원문보기

BMB reports, v.52 no.6, 2019년, pp.409 - 414

Ihn, Hye Jung (Institute for Hard Tissue and Bio-tooth Regeneration (IHBR), Kyungpook National University) , Kim, Tae Hoon (Department of Food Science and Biotechnology, Daegu University) , Kim, Kiryeong (Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University) , Kim, Gi-Young (Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University) , Jeon, You-Jin (Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University) , Choi, Yung Hyun (Department of Biochemistry, College of Korean Medicine, Dong-Eui University) , Bae, Jong-Sup (College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University) , Kim, Jung-Eun (Department of Molecular Medicine, School of Medicine, Kyungpook National University) , Park, Eui Kyun (Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University)

Abstract ▼ AI-Helper

Natural compounds isolated from medicinal herbs and plants have immense significance in maintaining bone health. Hydrolysable tannins have been shown to possess a variety of medicinal properties including antiviral, anticancer, and anti-osteoclastogenic activities. As a part of a study on the discovery of alternative agent against skeletal diseases, we isolated a hydrolysable tannin, 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-${\beta}$-D-glucose (DTOGG), from Galla Rhois and examined the effect on osteoclast formation and function. We found that DTOGG significantly inhibited receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation by downregulating the expression of the key regulator in osteoclastogenesis as well as osteoclast-related genes. Analysis of RANKL/RANK signaling revealed that DTOGG impaired activation of $I{\kappa}B{\alpha}$ and p65 in the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-${\kappa}B$) signaling pathway. Furthermore, DTOGG reduced bone resorbing activity of osteoclasts, compared to the vehicle-treated control. These results suggest that DTOGG could be a useful natural compound to manage osteoclast-mediated skeletal diseases.

주제어

AI 본문요약
AI-Helper

* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.

가설 설정

T˚Clarify whether DTOGG modulates the differentiation of BMMs into osteoclasts, BMMs were treated with DTOGG in the presence of M-CSF and RANKL. As expected, M-CSF and RANKL stimulated the formation of TRAP-positive multinucleated cells in the vehicle-treated control at day 4 (Fig.

제안 방법

Among them, tannins, polyphenolic compounds, have been reported to exhibit beneficial effects, such as antiviral, anticancer, and antioxidant effects (20-22). As a part of a study on the discovery of novel anti-osteoclastic drugs from natural products, we isolated DTOGG, a hydrolysable tannin, and examined its role in osteoclast formation and function.
To discover a natural alternative drug for osteolytic bone diseases, we examined the effect of DTOGG on RANKLmediated osteoclastogenesis in bone marrow-derived macrophages (BMMs) and the bone-resorbing function of mature osteoclasts. We further investigated the modes of action of DTOGG on osteoclast differentiation and function.
1D). We next evaluated the effect of DTOGG on the viability of BMMs t˚Confirm whether the antiosteoclastogenic effect of DTOGG was due to its cytotoxic activity. DTOGG at concentrations of up to 10 μM was not cytotoxic to murine BMMs (Fig.

대상 데이터

Six-week-old C57/B6L mice were obtained from Dae Han Bio Link (Chungbuk, Korea). All animal experiments were approved by the committees on the care and use of animals in research at Kyungpook National University, and were conducted in accordance with the guidelines for the care and use of laboratory animals.

데이터처리

Experiments were conducted three times, and all data are expressed as mean ± standard deviation (SD) and compared by the two-tailed Student’s t-test or one-way analysis of variance (ANOVA) with Tukey’s multiple comparison post-hoc test.

이론/모형

(B) BMMs were incubated with M-CSF (10 ng/ml) and different concentrations of DTOGG for 3 days. Cell viability was measured by the MTT assay. (C) Bone marrow-derived macrophages (BMMs) were cultured in osteoclastogenic medium containing M-CSF (10 ng/ml) and RANKL (20 ng/ml) in the presence of DTOGG (1, 5, or 10 μM) or vehicle.

성능/효과

Scale bar, 100 μm. (B) Resorption areas (left) were quantified using the i-Solution program, and the number of multinucleated osteoclasts (right) was scored. The results are representative of two independent experiments.

In conclusion, DTOGG suppressed RANKL-induced osteoclastogenesis and the bone-resorbing activity of osteoclasts. The key inhibitory mechanisms of DTOGG include the inhibition of RANKL-stimulated NF-ΚB signaling pathway and downregulation of NFATc1.

본문요약 정보가 도움이 되었나요? 예 아니오

참고문헌 (35)

Chambers TJ (2000) Regulation of the differentiation and function of osteoclasts. J Pathol 192, 4-13

상세보기

Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289, 1504-1508

상세보기

Boyle WJ, Simonet WS and Lacey DL (2003) Osteoclast differentiation and activation. Nature 423, 337-342

상세보기

Feng X and Teitelbaum SL (2013) Osteoclasts: New Insights. Bone Res 1, 11-26

상세보기

Takayanagi H, Kim S, Koga T et al (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3, 889-901

상세보기

Nakashima T and Takayanagi H (2011) New regulation mechanisms of osteoclast differentiation. Ann N Y Acad Sci 1240, E13-18

상세보기

Choi JG, Mun SH, Chahar HS et al (2014) Methyl gallate from Galla rhois successfully controls clinical isolates of Salmonella infection in both in vitro and in vivo systems. PLoS One 9, e102697

상세보기

Djakpo O and Yao W (2010) Rhus chinensis and Galla Chinensis--folklore to modern evidence: review. Phytother Res 24, 1739-1747

상세보기

Yim NH, Gu MJ, Hwang YH, Cho WK and Ma JY (2016) Water extract of Galla Rhois with steaming process enhances apoptotic cell death in human colon cancer cells. Integr Med Res 5, 284-292

상세보기

Kwon OJ, Bae JS, Lee HY et al (2013) Pancreatic lipase inhibitory gallotannins from Galla Rhois with inhibitory effects on adipocyte differentiation in 3T3-L1 cells. Molecules 18, 10629-10638

상세보기

Anandacoomarasamy A, Caterson I, Sambrook P, Fransen M and March L (2008) The impact of obesity on the musculoskeletal system. Int J Obes (Lond) 32, 211-222

상세보기

Hsu YH, Venners SA, Terwedow HA et al (2006) Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women. Am J Clin Nutr 83, 146-154

상세보기

Li J, Zeng L, Xie J et al (2015) Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops. Sci Rep 5, 17605

상세보기

Samuels JS, Shashidharamurthy R and Rayalam S (2018) Novel anti-obesity effects of beer hops compound xanthohumol: role of AMPK signaling pathway. Nutr Metab (Lond) 15, 42

상세보기

Choi SW, Kim SH, Lee KS et al (2017) Barley Seedling Extracts Inhibit RANKL-Induced Differentiation, Fusion, and Maturation of Osteoclasts in the Early-to-Late Stages of Osteoclastogenesis. Evid Based Complement Alternat Med 2017, 6072573

Matsubara T, Kokabu S, Nakatomi C et al (2018) The Actin-Binding Protein PPP1r18 Regulates Maturation, Actin Organization, and Bone Resorption Activity of Osteoclasts. Mol Cell Biol 38

상세보기

Asagiri M, Sato K, Usami T et al (2005) Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med 202, 1261-1269

상세보기

Wada T, Nakashima T, Hiroshi N and Penninger JM (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12, 17-25

상세보기

An J, Hao D, Zhang Q et al (2016) Natural products for treatment of bone erosive diseases: The effects and mechanisms on inhibiting osteoclastogenesis and bone resorption. Int Immunopharmacol 36, 118-131

상세보기

Cai Y, Zhang J, Chen NG et al (2017) Recent Advances in Anticancer Activities and Drug Delivery Systems of Tannins. Med Res Rev 37, 665-701

상세보기

Formagio AS, Volobuff CR, Santiago M, Cardoso CA, Vieira Mdo C and Valdevina Pereira Z (2014) Evaluation of Antioxidant Activity, Total Flavonoids, Tannins and Phenolic Compounds in Psychotria Leaf Extracts. Antioxidants (Basel) 3, 745-757

상세보기

Ueda K, Kawabata R, Irie T, Nakai Y, Tohya Y and Sakaguchi T (2013) Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses. PLoS One 8, e55343

상세보기

Yavropoulou MP and Yovos JG (2008) Osteoclastogenesis--current knowledge and future perspectives. J Musculoskelet Neuronal Interact 8, 204-216

Yagi M, Miyamoto T, Sawatani Y et al (2005) DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. J Exp Med 202, 345-351

상세보기

Gowen M, Lazner F, Dodds R et al (1999) Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res 14, 1654-1663

상세보기

Asagiri M and Takayanagi H (2007) The molecular understanding of osteoclast differentiation. Bone 40, 251-264

상세보기

Iotsova V, Caamano J, Loy J, Yang Y, Lewin A and Bravo R (1997) Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med 3, 1285-1289

상세보기

Boyce BF, Xing L, Franzoso G and Siebenlist U (1999) Required and nonessential functions of nuclear factor-kappa B in bone cells. Bone 25, 137-139

상세보기

Park EK, Kim MS, Lee SH et al (2004) Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation. Biochem Biophys Res Commun 325, 1472-1480

상세보기

Ihn HJ, Lee T, Kim JA et al (2017) OCLI-023, a Novel Pyrimidine Compound, Suppresses Osteoclastogenesis In Vitro and Alveolar Bone Resorption In Vivo. PLoS One 12, e0170159

상세보기

Ihn HJ, Lee T, Lee D et al (2018) A novel benzamide derivative protects ligature-induced alveolar bone erosion by inhibiting NFATc1-mediated osteoclastogenesis. Toxicol Appl Pharmacol 355, 9-17

상세보기

Kim JA, Choi YA, Yun HS, Bae YC, Shin HI and Park EK (2016) Extracellular calcium-binding peptide-modified ceramics stimulate regeneration of calvarial bone defects. Tissue Eng Regen Med 13, 57-65

상세보기

Imran KM, Yoon D, Lee TJ and Kim YS (2018) Medicarpin induces lipolysis via activation of Protein Kinase A in brown adipocytes. BMB Rep 51, 249-254

원문보기 상세보기

Jin SH, Kim H, Gu DR et al (2018) Actin-binding LIM protein 1 regulates receptor activator of $NF-{\kappa}B$ ligand-mediated osteoclast differentiation and motility. BMB Rep 51, 356-361

원문보기 상세보기

Ihn HJ, Kim JA, Bae YC, Shin HI, Baek MC and Park EK (2017) Afatinib ameliorates osteoclast differentiation and function through downregulation of RANK signaling pathways. BMB Rep 50, 150-155

원문보기 상세보기

이 논문을 인용한 문헌

저자의 다른 논문 :

연구과제 타임라인

LOADING...

LOADING...

LOADING...

LOADING...

LOADING...

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증