DOI QR코드

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Effects of Angelica sinensis Root on Longitudinal Bone Growth Rate in Adolescent Female Rats

  • Lee, Donghun (Kyung Hee University, College of Korean Medicine, Department of Herbal Pharmacology) ;
  • Kim, Hocheol (Kyung Hee University, College of Korean Medicine, Department of Herbal Pharmacology)
  • 투고 : 2016.11.17
  • 심사 : 2017.01.15
  • 발행 : 2017.01.30

초록

Objectives : This study aimed to investigate the effects of Angelicae sinensis Radix on longitudinal bone growth rate in rats. We have screened traditional medicinal herbs to develop the longitudinal bone growth stimulator by well-established rat model. A. sinensis was identified as one of the effective herbs in the screening process. Methods : Adolescent female rats were administered A. sinensis at doses of 30 mg/kg and 300 mg/kg for 10 consecutive days. To observe the rate of longitudinal bone growth, tetracycline was injected intraperitoneally on day 8 to stain a fluorescent band on the anew formed bone. To elucidate the mode of action, we observed insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) expression after A. sinensis administration in growth plate. Results : In the 300 mg/kg A. sinensis group, the length between the proximal endpoint of the tetracycline label and the division line between growth plate and bone was significantly increased compared with vehicle-treated control group. Height of the proximal tibial growth plate was higher in the A. sinensis group compared with control group. A. sinensis also upregulated the expressions of IGF-1 and BMP-2 in the proliferative zone and hypertrophic zone of the proximal tibial growth plate. Conclusions : A. sinensis increases longitudinal bone growth rate in rats. According to immunohistochemistry, A. sinensis increases local IGF-1 and BMP-2 expressions in the growth plate which can be considered as direct stimulation of GH on the local growth plate.

키워드

참고문헌

  1. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL. Chernausek, SD, Savage MO, Wit JM. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: A summary of the growth hormone research society, the lawson wilkins pediatric endocrine society, and the european society for paediatric endocrinology workshop. J Clin Endocrinol Metabol. 2008; 93: 4210-7. https://doi.org/10.1210/jc.2008-0509
  2. Downie AB, Mulligan J, Stratford RJ, Betts PR, Voss LD. Are short normal children at a disadvantage? The wessex growth study. Bmj. 1997; 314: 97-100. https://doi.org/10.1136/bmj.314.7074.97
  3. Stabler B, Clopper RR, Siegel PT, Stoppani C, Compton PG, Underwood LE. Academic achievement and psychological adjustment in short children. The national cooperative growth study. J Dev Behav Pediatr. 1994; 15: 1-6. https://doi.org/10.1097/00004703-199402000-00001
  4. Voss LD, Sandberg DE. The psychological burden of short stature: Evidence against. Eur J Endocrinol. 2004; 151: Suppl 1 S29-33. https://doi.org/10.1530/eje.0.151S029
  5. Zimet GD, Owens R, Dahms W, Cutler M, Litvene M, Cuttler L. Psychosocial outcome of children evaluated for short stature. Arch Pediatr Adolesc Med. 1997; 151: 1017-23. https://doi.org/10.1001/archpedi.1997.02170470051010
  6. Christensen TL, Djurhuus CB, Clayton P, Christiansen JS. An evaluation of the relationship between adult height and health-related quality of life in the general uk population. Clin Endocrinol. 2007; 67: 407-12. https://doi.org/10.1111/j.1365-2265.2007.02901.x
  7. Paajanen TA, Oksala NK, Kuukasjarvi P, Karhunen PJ. Short stature is associated with coronary heart disease: A systematic review of the literature and a meta-analysis. Eur Heart J. 2010; 31: 1802-9. https://doi.org/10.1093/eurheartj/ehq155
  8. Wannamethee SG, Shaper AG, Whincup PH, Walker M. Adult height stroke and coronary heart disease. Am J Epidemiol. 1998; 148: 1069-76. https://doi.org/10.1093/oxfordjournals.aje.a009584
  9. Hindmarsh PC, Dattani MT. Use of growth hormone in children. Nat Clin Pract Endocrinol Metab. 2006; 2: 260-8. https://doi.org/10.1038/ncpendmet0169
  10. Wit JM, Kamp GA, Rikken B. Spontaneous growth and response to growth hormone treatment in children with growth hormone deficiency and idiopathic short stature. Pediatr Res. 1996; 39 295-302.
  11. Hintz RL, Attie KM, Baptista J, Roche A. Effect of growth hormone treatment on adult height of children with idiopathic short stature Genentech collaborative group. N Engl J Med. 1999; 340: 502-7. https://doi.org/10.1056/NEJM199902183400702
  12. Leschek EW, Rose SR, Yanovski JA, Troendle JF, Quigley CA, Chipman JJ, Crowe BJ, Ross JL, Cassorla FG, Blum WF. Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: A randomized double-blind placebo-controlled trial. J Clin Endocrinol Metab. 2004; 89: 3140-8. https://doi.org/10.1210/jc.2003-031457
  13. August GP, Julius JR, Blethen SL. Adult height in children with growth hormone deficiency who are treated with biosynthetic growth hormone: The national cooperative growth study experience. Pediatrics. 1998; 102: 512-6.
  14. Bajpai A, Menon PS. Growth hormone therapy. Ind J Ped. 2005; 72: 139-44. https://doi.org/10.1007/BF02760699
  15. Bryant J, Baxter L, Cave CB, Milne R. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database Syst Rev. 2007; CD004440.
  16. Finkelstein BS, Imperiale TF, Speroff T, Marrero U, Radcliffe DJ, Cuttler L. Effect of growth hormone therapy on height in children with idiopathic short stature: A meta-analysis. Arch Pediatr Adolesc Med. 2002; 156: 230-40. https://doi.org/10.1001/archpedi.156.3.230
  17. Hintz RL. Growth hormone: Uses and abuses. Bmj. 2004; 328: 907-8. https://doi.org/10.1136/bmj.328.7445.907
  18. Silverman BL, Blethen SL, Reiter EO, Attie KM, Neuwirth RB, Ford KM. A long-acting human growth hormone (nutropin depot): Efficacy and safety following two years of treatment in children with growth hormone deficiency. J Pediatr Endocrinol. 2002; 15: Suppl 2 715-22.
  19. Leem K, Park SY, Lee DH, Kim H. Lovastatin increases longitudinal bone growth and bone morphogenetic protein-2 levels in the growth plate of sprague-dawley rats. Eur J Pediatr. 2002; 161: 406-7. https://doi.org/10.1007/s00431-002-0955-3
  20. Wen LW, Rui Z, Cai MG, Yan Q, Ling FH. Angelica sinensis in China-A review of botanical profile ethnopharmacology phytochemistry and chemical analysis. J Ethnopharmacol. 2016; 190: 116-41. https://doi.org/10.1016/j.jep.2016.05.023
  21. Gu ZR, Wang YL, Sun YJ, Ding JX. Simultaneous determination of five constituents in Angelica Sinensis from different areas and the quality evaluation. Chin Tradit Patent Med. 2014; 36: 2135-9.
  22. Yang Q, Populo SM, Zhang J, Yang G, Kodama H. Effect of Angelica sinensis on the proliferation of human bone cells. Clin Chim Acta. 2002; 324: 89-97. https://doi.org/10.1016/S0009-8981(02)00210-3
  23. Sims NA, Clement-Lacroix P, Da Ponte F, Bouali Y, Binart N, Moriggl R, Goffin V, Coschigano K, Gaillard-Kelly M, Kopchick J. Bone homeostasis in growth hormone receptor-null mice is restored by igf-i but independent of stat5. J Clin Invest. 2000; 106: 1095-103. https://doi.org/10.1172/JCI10753
  24. Yakar S, Rosen CJ. From mouse to man: Redefining the role of insulin-like growth factor-i in the acquisition of bone mass. Exp Biol Med. 2003; 228: 245-52. https://doi.org/10.1177/153537020322800302
  25. Hansson LI, Stenstrom A, Thorngren K. Skeletal deposition and toxicity of methacycline. Nature. 1968; 219: 624-5. https://doi.org/10.1038/219624a0
  26. Hunziker EB. Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes. Microsc Res Tech. 1994; 28: 505-19. https://doi.org/10.1002/jemt.1070280606
  27. Breur GJ, VanEnkevort BA, Farnum CE, Wilsman NJ. Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates. J Orthop Res. 1991; 9: 348-59. https://doi.org/10.1002/jor.1100090306
  28. Hansson LI. Daily growth in length of diaphysis measured by oxytetracycline in rabbit normally and after medullary plugging. Acta Orthop Scand. 1967; Suppl 101: 101+.
  29. Kuhn JL, DeLacey JH, Leenellett EE. Relationship between bone growth rate and hypertrophic chondrocyte volume in new zealand white rabbits of varying ages. J Orthop Res. 1996; 14: 706-11. https://doi.org/10.1002/jor.1100140505
  30. Hero M, Wickman S, Dunkel L. Treatment with the aromatase inhibitor letrozole during adolescence increases near-final height in boys with constitutional delay of puberty. Clin Endocrinol. 2006; 64: 510-3. https://doi.org/10.1111/j.1365-2265.2006.02499.x
  31. De Luca F, Barnes KM, Uyeda JA, De-Levi S, Abad V, Palese T, Mericq V, Baron J. Regulation of growth plate chondrogenesis by bone morphogenetic protein-2. Endocrinology. 2001; 142: 430-6. https://doi.org/10.1210/endo.142.1.7901
  32. Wu S, Yang W, De Luca F. Insulin-like growth factor-independent effects of growth hormone on growth plate chondrogenesis and longitudinal bone growth. Endocrinology. 2015; 156: 2541-51. https://doi.org/10.1210/en.2014-1983