천속단(Phlomis umbrosa Turcz)의 파골세포 분화에 미치는 영향
The Effects of Phlomis umbrosa Turcz on Osteoclast Differentiation
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초록
골다공증, 류마티스 관절염을 비롯한 많은 골질환은 파골세포의 지나친 골 흡수 활동으로 인하여 발생한다. 최근 들어, 천연물에서 추출한 성분을 이용하여 새로운 치료물질을 개발하기 위한 연구가 활발하게 진행되고 있다. 그 중, 천속단이라고 알려진 천연물질은 뼈를 튼튼하게 해주는 효능이 있는 것으로 알려져 있으나,천속단의 골질환과 관련된 정확한 효과나 치료기전에 대한 정보는 아직 알려진 바가 없다. 따라서 본 연구에서는 골수탐식세포에서 receptor activator of nuclear factor-κB ligand (RANKL)로 유도한 파골세포의 분화와 골 흡수능에 천속단이 어떠한 영향을 미치는지 알아보았다. 또한, 파골세포의 분화와 관련된 작용기전을 규명하였다. 본 실험에서 천속단은 RANKL로 유도한 파골세포의 분화와 골 흡수능을 현저히 억제하였고, RANKL과 macrophage-colony stimulating factor (M-CSF)를 처리한 골수탐식세포에서 NF-κB의 발현을 저해하였다. 더 나아가, c-Fos를 비롯한 nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP)의 mRNA 발현이 천속단에 의해 억제됨을 확인하였으며, 세포융합과 관련 있는 유전자인 Integrin αν, β3와 actin ring에 관여하는 유전자인 dendritic cell-specific transmembrane preotein (DC-STAMP)그리고 골 흡수능과 연관된 Cathepsin K 또한 같은 결과를 나타내었다. 이러한 결과는 천속단의 골다공증을 비롯한 골질환 치료의 후보물질로써의 가능성을 제시하였다.
Abstract
Many bone-related diseases such as osteoporosis, rheumatoid arthritis are occurred by excessive bone resorbing activity of osteoclasts. Recently, many studies have been proceeded to find out the new therapeutic materials from natural products of plants. Phlomis umbrosa Turcz, one of the natural products of plants has been known to improve bone health. However, the precise effects and treatment mechanisms of Phlomis umbrosa Turcz about bone diseases has been unknown. So, we examined the effects of Phlomis umbrosa Turcz on expression of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow-derived macrophages (BMMs) and bone resorption. Also, we investigated the treatment mechanisms of Phlomis umbrosa Turcz relating to osteoclast differentiation. Here, we showed that Phlomis umbrosa Turcz significantly suppressed RANKLinduced osteoclast differentiation and bone resportion. Furthermore, Phlomis umbrosa Turcz suppressed the activation of NF-κB in bone marrow macrophage treated RANKL and M-CSF. The mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP) in BMMs was inhibited by Phlomis umbrosa Turcz. Integrin αν, β3 relating to cell adhesion and dendritic cell-specific transmembrane protein (DC-STAMP) relating to the structure of filamentous actin (F-actin) ring and cathepsin K relating to bone resorbing activity are disrupted too. These results suggest that Phlomis umbrosa Turcz will be a good materials to treat bone diseases like osteoporosis.
참고문헌 (27)
- 박예수, "골다공증의 진단과 치료", 대한의사협회지, 55(11), pp.1083~1094 (2012), 대한의사협회
- Henriksen K, "Osteoclast activity and subtypes as a function of physiology and pathology-implications for future treatment of osteoporosis", Endocr Rev, 23, pp.31~63 (2011)
- David Roodman G, "Regulation of osteoclast differentiation", Ann NY Acad Sci, 1068, pp.100~109 (2006)
- Masataka A, "The molecular understanding of osteoclast differentiation", Bone, 40, pp.251~264 (2007)
- Lianping X, "Osteoclast precursors, RANKL", RANK, and immunology, 2005, pp.208, 19~29
- Andrea DF, "Osteoclast receptors and signaling", Arch Biochem Biophys, 473, pp.147~160 (2008)
- Soysa NS, "NF-κB functions in osteoclasts", Biochem Biophys Res Commun, 378, pp.1~5 (2009)
- Huang H, "Induction of c-Fos and NFATc1 during RANKL-stimulated osteoclast differentiation is mediated by the p38 signaling pathway", Biochem Biophys Res Commun, 351, pp.99~105 (2006)
- Cheng MH, "Osteoporosis treatment in postmenopausal women with pre-existing fracture", Taiwan J Obstet Gynecol, 51, pp.153~166 (2012)
- Sundeep K, "Bisphophonates-associated osteonecrosis of the jaw:report of a task force of the american society for bone and mineral research", J Bone Miner Res, 22, pp.1479~1491 (2007)
- Seo BI, "Hernal Medicine", Younglimsa
- Lee MS, "GM-CSF regulates fusion of mononuclear osteoclasts into bone-resorbing osteoclasts by activating the Ras", ERK pathway, 2009, pp.183, 3390~3399
- Kuhn DM, "Uses and Limitations of the XTT Assay in Studies of Candida Growth and Metabolism", J Clin Microbiol, 41, pp.506~508 (2003)
- Bradley EW, "Osteoclast culture and resorption assays", Methods Mol Biol, 455, pp.19~35 (2008)
- Delman PD, "Treatment of postmenopausal osteoporosis", Lancet, 359, pp.2018~2026 (2002)
- Kang MJ, "Bioavailability enhancing activities of natural compounds from medicinal plants", J Med Plant Res, 13, pp.1204~1211 (2009)
- 이명수, "파골세포 분화에 목향 물 추출물의 효과", 동의생리병리학회지, 25(3), pp.516~520 (2011), 대한동의병리학회
- 오재민, "파골세포 분화에 미치는 복분자 물 추출물의 효과", 동의생리병리학회지, 25(4), pp.669~673 (2011), 대한동의병리학회
- 리연, "오미자 물 추출물이 파골세포 분화에 미치는 영향", 동의생리병리학회지, 24(5), pp.848~853 (2010), 대한동의병리학회
- 김주호, "우슬의 파골세포 분화 억제와 골 흡수 억제효과", 대한본초학회지, 25(1), pp.65~74 (2010), 대한본초학회
- Yamamoto A, "Possible involvement of IκB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand", J Bone Miner Res, 17, pp.612~621 (2002)
- Wada T, "RANKLRANK signaling in osteoclastogenesis and bone disease", Trends Mol Med, 12, pp.17~25 (2006)
- Kim KS, "NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP)", Mol Endocrinol, 22, pp.176~185 (2008)
- Kim GS, "Association of the OSCAR promoter polymorphism with BMD in postmenopausal women", J Bone Miner Res, 20, pp.1342~1348 (2005)
- Nakamura I, "Involvement of alpha(v)beta3 integrins in osteoclast function", J Bone Miner Metab, 25, pp.337~344 (2007)
- Kukita T, "RANKL-induced DC-STAMP is essential for osteoclastogenesis", J Exp Med, 200, pp.941~946 (2004)
- Tanaka H, "Nicotine affects bone resorption and suppresses the expressions of Cathepsin K, MMP-9 and vacuolar- type(+)-ATPase d2 and organization in osteoclasts", PLoS One, 8, pp.59402~ (2013)