Effects of Cervi Parvum Cornu on Cell Cycle Regulation in Human Fetal Osteoblasts

녹용이 사람 태아 골모세포의 세포주기 조절에 미치는 영향

  • 양대승 (원광대학교 치과대학 치주과학교실) ;
  • 김현아 (원광대학교 치과대학 치주과학교실) ;
  • 현하나 (원광대학교 치과대학 치주과학교실) ;
  • 유형근 (원광대학교 치과대학 치주과학교실) ;
  • 김윤철 (원광대학교 약학대학) ;
  • 신형식 (원광대학교 치과대학 치주과학교실)
  • Published : 2002.12.31

Abstract

Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Cervi Parvum Comu(CPC) have been traditionally study as an hale, growth. hematogenous, anti-aging, hack pain in Eastern medicine. The purpose of present study was to investigate the effects of CPC extract on cell cycle progression and its molecular mechanism in human fetal osteoblasts. CPC extracts (10 ${\mu}g/ml$) increased cell proliferation in the human fetal osteoblasts compared to non-supplemented control. There was no significant change in the G1 and S phase, hut a increase in the G2/M phase in 10 ${\mu}g/ml$ and 100 ${\mu}g/ml$ of CPC extracts group as compared to non-supplemented control. The protein expression of cyclin E, cdk 2, cycln D, cdk 4, and cdk 6 was higher than that of control group. The level of p21 was lower than that of control. But that of pRb and pl6 was not distinguished from control. These results indicate that the increase of cell proliferation by CPC extracts may be due t o the increased expression of cyclin E, cdk 2, cyclin D, cdk 4 and cdk 6, and the decreased expression of p21 in human fetal osteoblasts.

Keywords

References

  1. 대한약전(1992) 6판. 한국 메디칼인텍스사
  2. 권혁세: 만병을 다스리는 민간약술 88, 제1판, 하나로, 서울, 1997;172-187
  3. 신국현, 이은방, 김재현, 정명숙, 조성익: 분말 녹용의 약물활성 연구(I). 생약학회지 1989;20: 180-187.
  4. 용재익: 實驗的 家兎負血에 미치는 塵茸投與의 影響. 약학회지 1964;8: 6-11
  5. Wang. B., Zhao. X., Qi, Yang, X., Koneko, S., Hattori, M., Namba, T. and Nomura, Y.: Stimulating effect of deer antler extract on protein synthesis in senescence-accelerated mice in Vivo. Chem Pharm Bull 1988;36: 2593-2598 https://doi.org/10.1248/cpb.36.2593
  6. Wang. B., Zhao. X., Qi, Koneko, S., Hattori, M., Namba, T. and Nomura, Y.: Effect of repeated administration of deer antler extract on biochemical changes related to aging in senescence-accelerated mice. Chem Pharm Bull 1988;36: 2587-2592 https://doi.org/10.1248/cpb.36.2587
  7. 허금, 최숙현, 이히빈, 정규찬, 고돈이: 塵茸에 關한 硏究(第2 報): 塵茸이 實驗用 白鼠의 成長에 미치는 影響에 對하여. 약학회지 1960;5: 10-15
  8. Ivankina NF, Isay SV, Busarova NG, Mischenko TY: Prostaglandin-like activity, fatty acid and Phospholipid composition of Sika deer(Cervus nippon) antlers at different growth stages. Comp Biochem PhysioI 1993;106: 159-162 https://doi.org/10.1016/0305-0491(93)90022-W
  9. Jhon GJ, Park SY, Han SY, Lee S, Kim Y, Chang YS: Studies of the chemical structure of ganglio-sides in Deer Antler, Cervus nippon. Chem pharm Bull 47: 1999;123-127 https://doi.org/10.1248/cpb.47.123
  10. Wang BX, Liu AJ, Cheng XJ, Wang QG, Wei GR, Cui JC: Anti-ulcer action of the polysaccharides isolated from pilose antler. Tao Hsueh Hsueh Pao 1985;20: 321-325
  11. Zhang ZQ Wang Y, Zhang H, Zhang W, Zhang Y, Wang BX: Anti-inflammatory effects of pilose antler peptide. Chung Kuo Yao Li Hsueh Pao 1994;15: 282-284
  12. Son NW, Shin MK, Lee HI: The effects of deer antler on the neuro response of starved mice. korean J Oriental Medicine 1986;7: 174-183
  13. Cho HJ, Jhon Gj: Changes of gangliosides metabolism in streptowotocin-induced diabetic rats and effet of deer antler. J Appl Pharm 1994;2: 223-228
  14. Park HS, Jhon GJ, Choi W: Deer antler extract selectively suppresses hyphal growth in dimorphic fungus, Candida albicans, J Microhiol BiothechnoI 1998;8: 291-294
  15. Van Der Eems KL, Brown RD, Gundberg CM: Circulating levels of 1,25 dihydroxyvitamin D, alkaline phosphatase, hydroxyproline, and osteocalcin associated with antler growth in white-tailed deer. Acta Endocrinol 1988;118: 407-414 https://doi.org/10.1677/joe.0.1180407
  16. Buhenik GA, Sempere AJ, Hamr J: Developing antlers, a model for endocrine regulation of hone growth. Concentration gradient of T3, T4, and alkaline phosphatase in the antlers, jugular, and the sapherous veins. Calcif Tissue Int 1987;41: 38-43 https://doi.org/10.1007/BF02555129
  17. Nurse, P.: Ordering S phase and M phase in the cell cycle, Cell 1994;79: 547-550 https://doi.org/10.1016/0092-8674(94)90539-8
  18. Sherr, C.: G1 phase progression.cycling on cue. Cell 1994;79: 551-555. https://doi.org/10.1016/0092-8674(94)90540-1
  19. Kato, J.A., Matsuoka, M., Strom, D, and Sherr, C.: Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol Cell Biol 1994;14: 2713-2721 https://doi.org/10.1128/MCB.14.4.2713
  20. 김 탁, 김재호, 피성희, 김은철, 유용욱, 유형근, 신형식: 니코틴이 치은섬유아세포의 세포주기 조절 단백질 발현에 미치는 영향. 대한치주과학회지 2001;30: 597-609
  21. 박영채, 양대승, 김재호, 김현아, 유용욱, 유형근, 신형식: 치은섬유아세포의 복제노화가 세포주기 조절에 미치는 영향. 대한치주과학회지 2001;31: 135-146
  22. 피성희, 김대겸, 김 탁, 유용욱, 유형근, 신형식: Cyclosporin A가 치은섬유아세포의 세포주기조절에 미치는 영향. 대한치주과학회지 2001;31: 611-622
  23. Sherr C. J.: Mammalian G1 cyclins, Cell 1993;73:1059-1065
  24. Serrano M., Hannon G,J., Beach D.: A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993;366:704-707 https://doi.org/10.1038/366704a0
  25. Bubenik GA, Smith PS: Circardian and circannual rhythms of melatonin in plasma of male white-tailed deer and the effect of oral administration of melatonin. J Exp ZooI 1987;241: 81-89 https://doi.org/10.1002/jez.1402410110
  26. Eiben B, Seharla S, Fischer K, Schmidt-Gayk H: Seasonal variations of serum 1,25-dihydroxyvitamin $D_3$ and alkaline phosphatase in relation to the antler formation in the fallow deer(Dama dama I).. Acta EndocrinoI 1984;107: 141-144
  27. Barling PM, Gupta DK, Lim CE: Involvement of Phosphodiesterase I in mineralization: histochemical studies using antler from red deer(Cervus elaphus) as a model. Calcif tissue Int 1999;65: 384-389 https://doi.org/10.1007/s002239900718
  28. Lincoln GA, Tyler NJ: Role of oestradiol in the regulation of the seasonal antler cycle in female reindeer, Rangifer tarandus, J Repred Fertil 1999;115: 167-174 https://doi.org/10.1530/jrf.0.1150167
  29. Price JS, Oyajobi BO, Oreffo RO, Russell RG: Cells cultured from the growing tip of red deer antler express alkaline phosphatase and proliferate in response to insuline-like growth factor-I, J EndocrinoI 1994;143: R9-16 https://doi.org/10.1677/joe.0.143R009
  30. Li C, Littlejohn RP, Suttie JM: Effects of insulin-like growth factor 1 and testosterone on the proliferation of antlergenic cells in vitro. J Exp Zool 1999;284:82-90 https://doi.org/10.1002/(SICI)1097-010X(19990615)284:1<82::AID-JEZ11>3.0.CO;2-K
  31. Lynch S.E., de Castilla G.R., Williams R.C., Kiristy C,P., Howell T.H., Reddy M.S., Antoniades H.N.: The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing, J PeriodontoI 1991;62: 458-467 https://doi.org/10.1902/jop.1991.62.7.458
  32. Sigurdsson T.J., Tatakis D,N., Lee M.B., Wikesjo U.M,: Periodontal regenerative potential of space-providing expanded polytetrafluoroethylene membranes and recombinant human bone morphogenetic proteins, J Periodontol 1995;66: 511-521 https://doi.org/10.1902/jop.1995.66.6.511
  33. Barboza E, Caula A, Machado F: Potential of recombinant human bone morphogenetic protein-2 in bone regeneration, Implant Dent 1999;8: 360-367 https://doi.org/10.1097/00008505-199904000-00006
  34. Ohlsson C, Vidal O: Effects of growth hormone and insulin-like growth factors on human osteoblasts. Eur J Clin invest 1998;28: 184-186 https://doi.org/10.1046/j.1365-2362.1998.00266.x
  35. Roth JA, Kim BG, Lin WL, Cho MI: Melatonin promotes osteoblast differentiation and bone formation, J Biol Chem 1999;274:22041-22047 https://doi.org/10.1074/jbc.274.31.22041
  36. Ernst M, Health JK, Schmid C, Froesch RE, Rodan GA: Evidence for a direct effect of estrogen on bone cells in vitro, J Steroid Biochem 1989;34: 279-284 https://doi.org/10.1016/0022-4731(89)90092-7
  37. Van Der Eems KL, Brown RD, Gundberg CM: Circulating levels of 1,25 dihydroxyvitamin D, alkaline phosphatase, hydroxyproline, and osteocalcin associated with antler growth in white-tailed deer. Acta Endocrinol 1988;118:407-414 https://doi.org/10.1677/joe.0.1180407
  38. Feng JQ, Chen D, Esparza J, Harris SE: Deer antler tissue contains two types of hone morphogenetic protain 4 mRNA transcripts. Biochim Biophys Acta 1995;1263: 163-168 https://doi.org/10.1016/0167-4781(95)00106-Q
  39. Bubenik GA, Smith PS: Circardian and circannual rhythms of melatonin in plasma of male white-tailed deer and the effect of oral administration of melatonin. J Exp Zool 1987;241: 81-89 https://doi.org/10.1002/jez.1402410110
  40. Lincoln GA, Tyler NJ: Role of oestradiol in the regulation of the seasonal antler cycle in female reindeer, Rangifer tarandus, J Repred Fertil 1999;115: 167-174 https://doi.org/10.1530/jrf.0.1150167
  41. 유윤정, 이현정, 임소형, 강정화, 이은희, 옥승호, 최봉규, 전길자: 녹용 추출물에 의한 MC3T3 세포의 분화촉진. 대한치주과학회지 2000;30: 885-893
  42. 윤기연, 유형근, 신형식. 녹각교가 치주인대세포의 세포 주기 조절에 미치는 영향. 원광대학교 치과대학 대학원 박사논문, 2002
  43. Waga, S., Hannon, G.J., and Beach, D. and Stillman B.: The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature (London) 1994;369: 574-578 https://doi.org/10.1038/369574a0
  44. Xiong, Y., Zhang, H. and Beach, D.: Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev 1993;7: 1572-1583 https://doi.org/10.1101/gad.7.8.1572
  45. Chen, X., Bargonetti, J. and Prives, C.: p53, through p21(WAF1/CIP1), induces cyclin D1 synthesis. Cancer Res 1995;55(10): 4257-4263