International Journal of Oral Biology

  • 제44권3호
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  • Pages.89-95
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  • 2019
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  • 1226-7155(pISSN)
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  • 2287-6618(eISSN)
대한구강생물학회 (The Korean Academy of Oral Biology)
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Piperlongumine suppressed osteoclastogenesis in RAW264.7 macrophages

  • Jin, Sun-Mi (Department of Oral and Maxillofacial Surgery, Pusan National University Dental Hospital) ;
  • Kang, Hae-Mi (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Park, Dan-Bi (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Yu, Su-Bin (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Kim, In-Ryoung (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Park, Bong-Soo (Department of Oral Anatomy, School of Dentistry, Pusan National University)
  • 투고 : 2019.08.08
  • 심사 : 2019.09.04
  • 발행 : 2019.09.30
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초록

Piperlongumine (PL) is a natural product found in long pepper (Piper longum). The pharmacological effects of PL are well known, and it has been used for pain, hepatoprotection, and asthma in Oriental medicine. No studies have examined the effects of PL on bone tissue or bone-related diseases, including osteoporosis. The current study investigated for the first time the inhibitory effects of PL on osteoclast differentiation, bone resorption, and osteoclastogenesis-related factors in RAW264.7 macrophages stimulated by the receptor activator for nuclear factor-${\kappa}B$ ligand (RANKL). Cytotoxicity was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and osteoclast differentiation and bone resorption were confirmed by tartrate-resistant acid phosphatase (TRAP) staining and pit formation analysis. Osteoclast differentiation factors were confirmed by western blotting. PL exhibited toxicity in RAW264.7 macrophages, inhibiting osteoclast formation and bone resorption, in addition to inhibiting the expression of osteoclastogenesis-related factors, such as tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Fos, and NFATc1, in RANKL-stimulated RAW264.7 macrophages. These findings suggest that PL is suitable for the treatment of osteoporosis, and it serves as a potential therapeutic agent for various bone diseases.

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참고문헌

  1. Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci 2006;1092:385-96. doi: 10.1196/annals.1365.035.
  2. Wu QY, Wang J, Tong X, Chen J, Wang B, Miao ZN, Li X, Ye JX, Yuan FL. Emerging role of circadian rhythm in bone remodeling. J Mol Med (Berl) 2019;97:19-24. doi: 10.1007/s00109-018-1723-9.
  3. O'Brien CA, Nakashima T, Takayanagi H. Osteocyte control of osteoclastogenesis. Bone 2013;54:258-63. doi: 10.1016/j.bone.2012.08.121.
  4. Rody WJ Jr, King GJ, Gu G. Osteoclast recruitment to sites of compression in orthodontic tooth movement. Am J Orthod Dentofacial Orthop 2001;120:477-89. doi: 10.1067/mod.2001.118623.
  5. Barrere F, van Blitterswijk CA, de Groot K. Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics. Int J Nanomedicine 2006;1:317-32.
  6. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-42. doi: 10.1038/nature01658.
  7. Long F. Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol 2012;13:27-38. doi: 10.1038/nrm3254.
  8. Qin L, Zhang G, Shi Y, Lee K, Leung P. Prevention and treatment of osteoporosis with trandiational herbal medicine. In: Deng H, editor. Current topics in osteoporosis. Hackensack: World Scientific; 2005. p. 513-31.
  9. Zhou ZL, Deng YF, Tao QS, Hu YF, Hou JF. Effects of Gushukang, a Chinese herbal medicine, on bone characteristics and osteoporosis in laying hens. Poult Sci 2009;88:2342-5. doi: 10.3382/ps.2009-00285.
  10. Guo Y, Li Y, Xue L, Severino RP, Gao S, Niu J, Qin LP, Zhang D, Bromme D. Salvia miltiorrhiza: an ancient Chinese herbal medicine as a source for anti-osteoporotic drugs. J Ethnopharmacol 2014;155:1401-16. doi: 10.1016/j.jep.2014.07.058.
  11. Wang ZQ, Li JL, Sun YL, Yao M, Gao J, Yang Z, Shi Q, Cui XJ, Wang YJ. Chinese herbal medicine for osteoporosis: a systematic review of randomized controlled trails. Evid Based Complement Alternat Med 2013;2013:356260. doi: 10.1155/2013/356260.
  12. Jin HO, Park JA, Kim HA, Chang YH, Hong YJ, Park IC, Lee JK. Piperlongumine downregulates the expression of HER family in breast cancer cells. Biochem Biophys Res Commun 2017;486:1083-9. doi: 10.1016/j.bbrc.2017.03.166.
  13. Chatterjee A, Dutta CP. Alkaloids of Piper longum Linn. I. Structure and synthesis of piperlongumine and piperlonguminine. Tetrahedron 1967;23:1769-81. doi: 10.1016/S0040-4020(01)82575-8.
  14. Wang F, Mao Y, You Q, Hua D, Cai D. Piperlongumine induces apoptosis and autophagy in human lung cancer cells through inhibition of PI3K/Akt/mTOR pathway. Int J Immunopathol Pharmacol 2015;28:362-73. doi: 10.1177/0394632015598849.
  15. Kumar S, Kamboj J, Suman, Sharma S. Overview for various aspects of the health benefits of Piper longum linn. fruit. J Acupunct Meridian Stud 2011;4:134-40. doi: 10.1016/S2005-2901(11)60020-4.
  16. Yu SB, Kim HJ, Kang HM, Park BS, Lee JH, Kim IR. Cordycepin accelerates osteoblast mineralization and attenuates osteoclast differentiation in vitro. Evid Based Complement Alternat Med 2018;2018:5892957. doi: 10.1155/2018/5892957.
  17. Che CT, Wong MS, Lam CW. Natural products from Chinese medicines with potential benefits to bone health. Molecules 2016;21:239. doi: 10.3390/molecules21030239.
  18. An J, Yang H, Zhang Q, Liu C, Zhao J, Zhang L, Chen B. Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation. Life Sci 2016;147:46-58. doi: 10.1016/j.lfs.2016.01.024.
  19. Wang T, Liu Q, Tjhioe W, Zhao J, Lu A, Zhang G, Tan RX, Zhou M, Xu J, Feng HT. Therapeutic potential and outlook of alternative medicine for osteoporosis. Curr Drug Targets 2017;18:1051-68. doi: 10.2174/1389450118666170321105425.
  20. Ming LG, Chen KM, Xian CJ. Functions and action mechanisms of flavonoids genistein and icariin in regulating bone remodeling. J Cell Physiol 2013;228:513-21. doi: 10.1002/jcp.24158.
  21. Wu L, Ling Z, Feng X, Mao C, Xu Z. Herb medicines against osteoporosis: active compounds & relevant biological mechanisms. Curr Top Med Chem 2017;17:1670-91. doi: 10.2174/1568026617666161116141033.
  22. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-64. doi: 10.1056/NEJMra030831.
  23. Teitelbaum SL. Bone resorption by osteoclasts. Science 2000;289:1504-8. doi: 10.1126/science.289.5484.1504.
  24. Filgueira L. Fluorescence-based staining for tartrate-resistant acidic phosphatase (TRAP) in osteoclasts combined with other fluorescent dyes and protocols. J Histochem Cytochem 2004;52:411-4. doi: 10.1177/002215540405200312.
  25. Hayman AR. Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. Autoimmunity 2008;41:218-23. doi: 10.1080/08916930701694667.
  26. Hayman AR, Bune AJ, Bradley JR, Rashbass J, Cox TM. Osteoclastic tartrate-resistant acid phosphatase (Acp 5): its localization to dendritic cells and diverse murine tissues. J Histochem Cytochem 2000;48:219-28. doi: 10.1177/002215540004800207.
  27. Takayanagi H. The role of NFAT in osteoclast formation. Ann N Y Acad Sci 2007;1116:227-37. doi: 10.1196/annals.1402.071.