CELLMED (셀메드)

Cellmed Orthocellular Medicine and Pharmaceutical Association (셀메드 세포교정의약학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of the Fraction of Sambucus Williamsii, NNMBS 246, on Osteoblastic Differentiation

  • Kang, Soon-Il (Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University) ;
  • Park, Jaesuh (Department of Dentistry, Graduate School, Kyung Hee University) ;
  • Kwon, Il-Keun (Department of Dental Materials, School of Dentistry, Kyung Hee University) ;
  • Kim, Eun-Cheol (Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University)
  • Received : 2018.07.17
  • Accepted : 2018.07.30
  • Published : 2018.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone formation. The purpose of this study was to examine the effects of NNMBS 246 osteoblastic differentiation with associated signaling pathways. NNMBS 246 markedly increased alkaline phosphatase (ALP) activity and calcium nodule formation. Stimulation with NNMBS 246 not only increased the differentiation markers (ALP, OPN, OCN) level and transcription markers (RUNX2, Osterix) mRNA expression but also upregulated the ECM molecules and OPG mRNA expression. Treatments of NNMBS 246 downregulated MMPs (MMP-1, MMP-2, MMP-9), but RANKL mRNA expression. Furthermore, NNMBS 246 activated osteoblastic differentiation markers and formed calcium nodules in human periodontal ligament cells (hPDLCs) and cementoblast cells. NNMBS 246 induced phosphorylation of MAPKs, Akt, nuclear p65 and IkB-${\alpha}$. BMP-2/Smad and ${\beta}$-catenin signaling pathways were activated by NNMBS 246. Sirtinol (SIRT1 inhibitor) inhibited NNMBS 246-induced osteoblastic differentiation markers mRNA expression. These results suggested that NNMBS 246 has the potential to enhance osteoblastogenesis probably through the activation of BMP/Smad and ${\beta}$-catenin signal pathways, and SIRT1 plays as critical mediator in bone anabolic effect of NNMBS 246.

Keywords

References

  1. Backesjo CM, Li Y, Lindgren U, Haldosen LA. Activation of Sirt1 decrease adipocyte formation during osteoblast differentiation of mesenchymal stem cells. J Bone Miner Res 2006;21:993-1002. https://doi.org/10.1359/jbmr.060415
  2. Bai L, Pang WJ, Yang YJ, Yang GS. Modulation of Sirt1 by resveratrol and nicotinamide alters proliferation and differentiation of pig preadipocytes. Mol Cell Biochem 2008;307:129-140.
  3. Bartold PM, McCulloch CA, Narayanan AS, Pitaru S. Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology. Periodontol 2000 2000;(24):253-69.
  4. Blander G, Bhimavarapu A, Mammone T, et al. SIRT1 promotes differentiation of normal human keratinocytes. J Invest Dermatol 2009;129:41-49. https://doi.org/10.1038/jid.2008.179
  5. Bolander ME. Regulation of fracture repair by growth factors. Proc Soc Exp Biol Med. 1992;200:165-70. https://doi.org/10.3181/00379727-200-43410A
  6. Dai Z, Li Y, Quarles LD et al. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine 2007;14:806-814. https://doi.org/10.1016/j.phymed.2007.04.003
  7. De Biase P, Capanna R. Clinical applications of BMPs. Injury. 2005 ;36 Suppl 3:S43-6. https://doi.org/10.1016/j.injury.2005.07.034
  8. Eliseev RA, Schwarz EM, Zuscik MJ et al. Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NF-kB. Exp Cell Res 2006;312:40-50. https://doi.org/10.1016/j.yexcr.2005.09.016
  9. Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle, Mol. Cell Biol. 2003;23:3173-3185.
  10. Fujita T, Azuma Y, Fukuyama R et al. Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3-Akt signaling. J Cell Biol 2004;166:85-95. https://doi.org/10.1083/jcb.200401138
  11. Fulco M, Schiltz RL, Iezzi S, et al. Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. Mol Cell 2003;12:51-62. https://doi.org/10.1016/S1097-2765(03)00226-0
  12. Hassumi MY, Silva-Filho VJ, Campos-Junior JC, Vieira SM, Cunha FQ, Alves PM, Alves JB, Kawai T, Goncalves RB, Napimoga MH. PPAR-gamma agonist rosiglitazone prevents inflammatory periodontal bone loss by inhibiting osteoclastogenesis. 2009; 9:1150-8. https://doi.org/10.1016/j.intimp.2009.06.002
  13. Hisahara S, Chiba S, Matsumoto H, et al.. Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. 2008;105:15599-15604. https://doi.org/10.1073/pnas.0800612105
  14. Inanc B, Elcin AE, Elcin YM. Osteogenic induction of human periodontal ligament fibroblasts under two- and threedimensional culture conditions. Tissue Eng 2006;12:257-266. https://doi.org/10.1089/ten.2006.12.257
  15. Jeong GS, Lee SH, Jeong SN, Kim YC, Kim EC. Antiinflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1.IntImmunopharmacol. 2009;9:1374-80.
  16. Jeong GS, Lee DS, Li B, Lee HJ, Kim EC, Kim YC. Effects of sappanchalcone on the cytoprotection and anti-inflammation via heme oxygenase-1 in human pulp and periodontal ligament cells.Eur J Pharmacol. 2010 ;644:230-7. https://doi.org/10.1016/j.ejphar.2010.06.059
  17. Karring T, Nyman S, Gottlow J, Laurell L. Development of the biological concept of guided tissue regenerationeanimal and human studies. Periodontol 2000 1993;1:26-35. https://doi.org/10.1111/j.1600-0757.1993.tb00204.x
  18. Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux NY, et al. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol 2006;169:987-98. https://doi.org/10.2353/ajpath.2006.060180
  19. Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling.J Clin Invest. 2006;116:1202-9. https://doi.org/10.1172/JCI28551
  20. Kumar A, Sharma SS. NF-kappaB inhibitory action of resveratrol: a probable mechanism of neuroprotection in experimental diabetic neuropathy. BiochemBiophys Res Commun 2010;394:360-365. https://doi.org/10.1016/j.bbrc.2010.03.014
  21. Lee FS, Hagler J, Chen ZJ, Maniatis T. Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway. Cell 1997;88:213-222. https://doi.org/10.1016/S0092-8674(00)81842-5
  22. Lee KS, Kim HJ, Li QL, Chi XZ, Ueta C, Komori T, Wozney JM, Kim EG, Choi JY, Ryoo HM, Bae SC. Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol. 2000;20:8783-92. https://doi.org/10.1128/MCB.20.23.8783-8792.2000
  23. Lee TB. Coloured Flora of Korea, Vol. 2, Hyang-Moon Sa, Seoul 1998:229.
  24. Lieberman JR, Daluiski A, Einhorn TA. The role of growth factors in the repair of bone.Biology and clinical applications. J Bone Joint Surg Am 2002;84-A:1032-44.
  25. Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T. JNK Activity Is Essential for Atf4 Expression and Late-Stage Osteoblast Differentiation. J Bone Miner Res 2009;24:398-410. https://doi.org/10.1359/jbmr.081107
  26. Miyamoto T, Suda T. Differentiation and function of osteoclasts. Keio J Med. 2003;52:1-7. https://doi.org/10.2302/kjm.52.1
  27. Mizutani K, Ikeda K, Kawai Y, Yamori Y. Resveratrol stimulates the proliferationand differentiation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun1998;253:859-863. https://doi.org/10.1006/bbrc.1998.9870
  28. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G. Stimulation of bone formation in vitro and in rodents by statins.Science. 1999;286:1946-9. https://doi.org/10.1126/science.286.5446.1946
  29. Nohe A, Keating E, Knaus P, Petersen NO. Signal transduction of bone morphogenetic protein receptors. Cell Signal. 2004;16:291-9. https://doi.org/10.1016/j.cellsig.2003.08.011
  30. Ota H, Tokunaga E, Chang K et al. Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 2006;25:176-185. https://doi.org/10.1038/sj.onc.1209049
  31. Picard F, Kurtev M, Chung N, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature2004;429:771-776. https://doi.org/10.1038/nature02583
  32. Prince M, Banerjee C, Javed A, Green J, Lian JB, Stein GS, Bodine PV, Komm BS. Expression and regulation of Runx2/Cbfa1 and osteoblast phenotypic markers during the growth and differentiation of human osteoblasts.J Cell Biochem. 2001;80:424-40. https://doi.org/10.1002/1097-4644(20010301)80:3<424::AID-JCB160>3.0.CO;2-6
  33. Ripamonti U, Reddi AH. Periodontal regeneration: potential role of bone morphogenetic proteins. J Periodont Res 1994;29:225-35. https://doi.org/10.1111/j.1600-0765.1994.tb01216.x
  34. Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ. Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res 2007;86:306-19. https://doi.org/10.1177/154405910708600403
  35. Tissenbaum HA, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditiselegans, Nature 2001;410: 227-230. https://doi.org/10.1038/35065638
  36. Wang Z, Han H, Yang B, Xia Y, Kuang H. Two New Iridoid Glycosides from the Root Barks of Sambucus williamsii. Hance Molecules 2011;16(5):3869-3874 https://doi.org/10.3390/molecules16053869
  37. Xiao H, Dai Y, Wong M, Yao X. Synthesis and photophysical properties of a novel pyridinium salt based on dipicolinate. Fitoterapia 2014;94:29 https://doi.org/10.1016/j.fitote.2014.01.012
  38. Xie F, Wu CF, Zhang Y, Yao XS, Cheung PY, Chan AS. Increase in bone mass and bone strength by Sambucus williamsii HANCE in ovariectomized rats. Biol Pharm Bull. 2005;28:1879-85. https://doi.org/10.1248/bpb.28.1879
  39. Yamamoto N, Akiyama S, Katagiri T, Namiki M, Kurokawa T, Suda T. Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts. Biochem Biophys Res Commun. 1997;238:574-80. https://doi.org/10.1006/bbrc.1997.7325
  40. Youn J, Lee JS, Na HK, Kundu JK, Surh YJ. Resveratrol and piceatannol inhibit iNOS expression and NF-kappaB activation in dextran sulfate sodium-induced mouse colitis. Nutr Cancer 2009;61:847-854. https://doi.org/10.1080/01635580903285072
  41. Yun JH, Pang EK, Kim CS, Yoo YJ, Cho KS, Chai JK, Kim CK, Choi SH.Inhibitory effects of green tea polyphenol (-)-epigallocatechingallate on the expression of matrix metalloproteinase-9 and on the formation of osteoclasts. J 2004;39:300-7. https://doi.org/10.1111/j.1600-0765.2004.00743.x
  42. Zhao H, Alexeev A, Sharma V, Guzman LD, Bojanowski K. Effect of SBD.4A--a defined multicomponent preparation of Angelica sinensis--in periodontal regeneration models.Ph 2008 ;22:923-8. https://doi.org/10.1002/ptr.2421
  43. Zhang RH, Qiu HM. Acta Chin. Med. Pharmacol. 1997;4:30.