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Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat

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Abstract

This study was performed to evaluate the possible protective effect of two calcium channel blocker’s “lacidipine (LAC) and amlodipine (AML)” on bone metabolism in an experimental ovariectomized and inflammation-induced osteoporosis rat model (OVXinf). For the purpose of this study, the rats were divided into eight groups, each containing eight rats: sham-operated control (group 1, SH), sham + inflammation (group 2, SHinf), ovariectomy (group 3, OVX), ovariectomy + inflammation (group 4, OVXinf), ovariectomy + LAC 4 mg/kg (group 5, OVX + LAC), ovariectomy + inflammation + LAC 4 mg/kg (group 6, OVXinf + LAC), ovariectomy + AML 5 mg/kg (group 7, OVX + AML), ovariectomy + inflammation + AML 5 mg/kg (group 8, OVXinf + AML). The levels of osteocalcin and osteopontin decreased in OVXinf + LAC and OVXinf + AML groups. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. Gene expression levels of the osteogenic factor runt-related transcription factor 2 (Runx2) and type I collagen 1A1 (Col1A1) significantly decreased in the OVXinf group, when compared with the control group. AML or LAC administrations increased the levels of Runx2 and Col1A1. These results suggest that amlodipine and lacidipine may be a novel therapeutic target for radical osteoporosis treatment in hypertensive patients.

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References

  1. Abernethy, D.R., and J.B. Schwartz. 1999. Calcium-antagonist drugs. The New England Journal of Medicine 341: 1447–57.

    Article  CAS  PubMed  Google Scholar 

  2. Rosenkranz, A.C., H. Lob, T. Breitenbach, R. Berkels, and R. Roesen. 2006. Endothelial antioxidant actions of dihydropyridines and angiotensin converting enzyme inhibitors. European Journal of Pharmacology 529: 55–62.

    Article  CAS  PubMed  Google Scholar 

  3. Suleyman, H., Z. Halici, A. Hacimuftuoglu, and F. Gocer. 2006. Role of adrenal gland hormones in antiinflammatory effect of calcium channel blockers. Pharmacological Reports 58: 692–9.

    CAS  PubMed  Google Scholar 

  4. Albayrak, A., Y. Bayir, Z. Halici, E. Karakus, A. Oral, M.S. Keles, et al. 2013. The biochemical and histopathological investigation of amlodipine in ethylene glycol-induced urolithiasis rat model. Renal Failure 35: 126–31.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang, X., and T.H. Hintze. 1998. Amlodipine releases nitric oxide from canine coronary microvessels: an unexpected mechanism of action of a calcium channel-blocking agent. Circulation 97: 576–80.

    Article  CAS  PubMed  Google Scholar 

  6. Cominacini, L., A.F. Pasini, A.M. Pastorino, U. Garbin, A. Davoli, A. Rigoni, et al. 1999. Comparative effects of different dihydropyridines on the expression of adhesion molecules induced by TNF-Α-alpha on endothelial cells. Journal of Hypertension 17: 1837–41.

    Article  CAS  PubMed  Google Scholar 

  7. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 2000; 17:1-45.

  8. Melton 3rd, L.J., E.A. Chrischilles, C. Cooper, A.W. Lane, and B.L. Riggs. 1992. Perspective. How many women have osteoporosis? Journal of Bone and Mineral Research : the official Journal of the American Society for Bone and Mineral Research 7: 1005–10.

    Article  Google Scholar 

  9. Parfitt AM. Skeletal heterogeneity and the purposes of bone remodelling: implications for the understanding of osteoporosis. In: Marcus R, Zfeldman D, Kelsey J, eds. Osteoporosis. San Diego: Academic Press, 2000

  10. Libby, P., P.M. Ridker, and A. Maseri. 2002. Inflammation and atherosclerosis. Circulation 105: 1135–43.

    Article  CAS  PubMed  Google Scholar 

  11. Liehr, J.G. 1996. Antioxidant and prooxidant properties of estrogens. Journal of Laboratory and Clinical Medicine 128: 344–5.

    Article  CAS  PubMed  Google Scholar 

  12. Cuzzocrea, S., E. Mazzon, L. Sautebin, I. Serraino, L. Dugo, G. Calabro, et al. 2001. The protective role of endogenous estrogens in carrageenan-induced lung injury in the rat. Molecular Medicine 7: 478–87.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Pacifici, R. 1995. Cytokines and osteoclast activity. Calcified Tissue International 56(Suppl 1): S27–8.

    Article  CAS  Google Scholar 

  14. Pfeilschifter, J., C. Chenu, A. Bird, G.R. Mundy, and G.D. Roodman. 1989. Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. Journal of Bone and Mineral Research The official journal of the American Society for Bone and Mineral Research 4: 113–8.

    Article  CAS  Google Scholar 

  15. Polat, B., Z. Halici, E. Cadirci, A. Albayrak, E. Karakus, Y. Bayir, et al. 2013. The effect of alpha-lipoic acid in ovariectomy and inflammation-mediated osteoporosis on the skeletal status of rat bone. European Journal of Pharmacology 718: 469–74.

    Article  CAS  PubMed  Google Scholar 

  16. Avsar, U., E. Karakus, Z. Halici, Y. Bayir, H. Bilen, A. Aydin, et al. 2013. Prevention of bone loss by Panax ginseng in a rat model of inflammation-induced bone loss. Cellular and Molecular Biology (Noisy-le-Grand, France) 59(Suppl): OL1835–41.

    Google Scholar 

  17. Mody, N., F. Parhami, T.A. Sarafian, and L.L. Demer. 2001. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radical Biology and Medicine 31: 509–19.

    Article  CAS  PubMed  Google Scholar 

  18. Ahlborg, H.G., O. Johnell, and M.K. Karlsson. 2004. Long term effects of oestrogen therapy on bone loss in postmenopausal women: a 23 year prospective study. BJOG 111: 335–9.

    Article  CAS  PubMed  Google Scholar 

  19. Rossouw, J.E., G.L. Anderson, R.L. Prentice, A.Z. LaCroix, C. Kooperberg, M.L. Stefanick, et al. 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 288: 321–33.

    Article  CAS  PubMed  Google Scholar 

  20. Rachner, T.D., S. Khosla, and L.C. Hofbauer. 2011. Osteoporosis: now and the future. Lancet 377: 1276–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Gallagher, J.C., C.M. Jerpbak, W.S. Jee, K.A. Johnson, H.F. DeLuca, and B.L. Riggs. 1982. 1,25-Dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis. Proceedings of the National Academy of Sciences of the United States of America 79: 3325–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Masuyama, R., J. Vriens, T. Voets, Y. Karashima, G. Owsianik, R. Vennekens, et al. 2008. TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metabolism 8: 257–65.

    Article  CAS  PubMed  Google Scholar 

  23. Krempien, B., S. Vukicevic, M. Vogel, A. Stavljenic, and R. Buchele. 1988. Cellular basis of inflammation-induced osteopenia in growing rats. Journal of bone and mineral research The Official Journal of the American Society for Bone and Mineral Research 3: 573–82.

    Article  CAS  Google Scholar 

  24. Puel, C., A. Quintin, J. Mathey, C. Obled, M.J. Davicco, P. Lebecque, et al. 2005. Prevention of bone loss by phloridzin, an apple polyphenol, in ovariectomized rats under inflammation conditions. Calcified Tissue International 77: 311–8.

    Article  CAS  PubMed  Google Scholar 

  25. Dursun, H., F. Albayrak, A. Uyanik, N.O. Keles, P. Beyzagul, E. Bayram, et al. 2010. Effects of hypertension and ovariectomy on rat hepatocytes. Are amlodipine and lacidipine protective? (A stereological and histological study). The Turkish Journal of Gastroenterology The Official Journal of Turkish Society of Gastroenterology 21: 387–95.

    PubMed  Google Scholar 

  26. Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25: 402–408.

    Article  CAS  PubMed  Google Scholar 

  27. Frost, H.M., and W.S. Jee. 1992. On the rat model of human osteopenias and osteoporoses. Bone and Mineral 18: 227–36.

    Article  CAS  PubMed  Google Scholar 

  28. Lindsay, R. 1993. Prevention and treatment of osteoporosis. Lancet 341: 801–5.

    Article  CAS  PubMed  Google Scholar 

  29. Pfeilschifter, J., C. Wuster, M. Vogel, B. Enderes, R. Ziegler, and H.W. Minne. 1987. Inflammation-mediated osteopenia (IMO) during acute inflammation in rats is due to a transient inhibition of bone formation. Calcified Tissue International 41: 321–5.

    Article  CAS  PubMed  Google Scholar 

  30. Lee, N.K., H. Sowa, E. Hinoi, M. Ferron, J.D. Ahn, C. Confavreux, et al. 2007. Endocrine regulation of energy metabolism by the skeleton. Cell 130: 456–69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Pacifici, R. 1996. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. Journal of Bone and Mineral Research The Official Journal of the American Society for Bone and Mineral Research 11: 1043–51.

    Article  CAS  Google Scholar 

  32. Hughes, D.E., A. Dai, J.C. Tiffee, H.H. Li, G.R. Mundy, and B.F. Boyce. 1996. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta. Nature Medicine 2: 1132–6.

    Article  CAS  PubMed  Google Scholar 

  33. Oursler, M.J., P. Osdoby, J. Pyfferoen, B.L. Riggs, and T.C. Spelsberg. 1991. Avian osteoclasts as estrogen target cells. Proceedings of the National Academy of Sciences of the United States of America 88: 6613–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Manolagas, S.C., and R.L. Jilka. 1995. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. The New England Journal of Medicine 332: 305–11.

    Article  CAS  PubMed  Google Scholar 

  35. Foskett, J.K., C. White, K.H. Cheung, and D.O. Mak. 2007. Inositol trisphosphate receptor Ca2+ release channels. Physiological Reviews 87: 593–658.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Blair, H.C., P.H. Schlesinger, C.L. Huang, and M. Zaidi. 2007. Calcium signalling and calcium transport in bone disease. Subcellular Biochemistry 45: 539–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Morikawa, K., T. Goto, A. Tanimura, S. Kobayashi, and K. Maki. 2008. Distribution of inositol 1,4,5-trisphosphate receptors in rat osteoclasts. Acta Histochemistry Cytochemistry 41: 7–13.

    Article  CAS  Google Scholar 

  38. Mentaverri R, Yano S, Chattopadhyay N, Petit L, Kifor O, Kamel S, et al. 2006. The calcium sensing receptor is directly involved in both osteoclast differentiation and apoptosis. Faseb J 20:2562-+.

  39. Kuroda, Y., C. Hisatsune, T. Nakamura, K. Matsuo, and K. Mikoshiba. 2008. Osteoblasts induce Ca2+ oscillation-independent NFATc1 activation during osteoclastogenesis. Proceedings of the National Academy of Sciences of the United States of America 105: 8643–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Abou-Saleh, H., A.R. Pathan, A. Daalis, S. Hubrack, H. Abou-Jassoum, H. Al-Naeimi, et al. 2013. Inositol 1,4,5-trisphosphate (ip3) receptor up-regulation in hypertension is associated with sensitization of Ca2+ release and vascular smooth muscle contractility. Journal of Biological Chemistry 288: 32941–32951.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Berridge, M.J. 1993. Inositol trisphosphate and calcium signalling. Nature 361: 315–25.

    Article  CAS  PubMed  Google Scholar 

  42. Seibel, M.J. 2006. Biochemical markers of bone turnover part II: clinical applications in the management of osteoporosis. Clinical Biochemistry Reviews 27: 123–38.

    Google Scholar 

  43. Ducy, P., C. Desbois, B. Boyce, G. Pinero, B. Story, C. Dunstan, et al. 1996. Increased bone formation in osteocalcin-deficient mice. Nature 382: 448–52.

    Article  CAS  PubMed  Google Scholar 

  44. Lian, J.B., M. Tassinari, and J. Glowacki. 1984. Resorption of implanted bone prepared from normal and warfarin-treated rats. Journal of Clinical Investigation 73: 1223–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Ingram, R.T., Y.K. Park, B.L. Clarke, and L.A. Fitzpatrick. 1994. Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling. Journal of Clinical Investigation 93: 989–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Hofbauer, L.C., F. Gori, B.L. Riggs, D.L. Lacey, C.R. Dunstan, T.C. Spelsberg, et al. 1999. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140: 4382–9.

    CAS  PubMed  Google Scholar 

  47. Filip, R.S., and J. Zagorski. 2004. Age- and BMD-related differences in biochemical markers of bone metabolism in rural and urban women from Lublin Region, Poland. Annals of Agricultural and Environmental Medicine 11: 255–9.

    PubMed  Google Scholar 

  48. Feng, J., S. Liu, S. Ma, J. Zhao, W. Zhang, W. Qi, et al. 2014. Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-kappaB signaling pathway. Acta Biochimica Biophysica Sinica (Shanghai) 46: 1024–33.

    Article  Google Scholar 

  49. Choi, S.T., J.H. Kim, E.J. Kang, S.W. Lee, M.C. Park, Y.B. Park, et al. 2008. Osteopontin might be involved in bone remodelling rather than in inflammation in ankylosing spondylitis. Rheumatology 47: 1775–1779.

    Article  CAS  PubMed  Google Scholar 

  50. Standal, T., M. Borset, and A. Sundan. 2004. Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Experimental Oncology 26: 179–84.

    CAS  PubMed  Google Scholar 

  51. Chang, I.C., T.I. Chiang, K.T. Yeh, H. Lee, and Y.W. Cheng. 2010. Increased serum osteopontin is a risk factor for osteoporosis in menopausal women. Osteoporosis International 21: 1401–1409.

    Article  CAS  PubMed  Google Scholar 

  52. Yoshitake, H., S.R. Rittling, D.T. Denhardt, and M. Noda. 1999. Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption. Proceedings of the National Academy of Sciences of the United States of America 96: 8156–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Kavukcuoglu, N.B., D.T. Denhardt, N. Guzelsu, and A.B. Mann. 2007. Osteopontin deficiency and aging on nanomechanics of mouse bone. Journal of Biomedical Materials Research. Part A 83A: 136–144.

    Article  CAS  Google Scholar 

  54. Kwak, J., J.N. Zara, M. Chiang, R. Ngo, J. Shen, A.W. James, et al. 2013. NELL-1 injection maintains long-bone quantity and quality in an ovariectomy-induced osteoporotic senile rat model. Tissue Engineering Part A 19: 426–36.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Notoya, M., R. Arai, T. Katafuchi, N. Minamino, and H. Hagiwara. 2007. A novel member of the calcitonin gene-related peptide family, calcitonin receptor-stimulating peptide, inhibits the formation and activity of osteoclasts. European Journal of Pharmacology 560: 234–239.

    Article  CAS  PubMed  Google Scholar 

  56. Jilka, R.L. 1998. Cytokines, bone remodeling, and estrogen deficiency: a 1998 update. Bone 23: 75–81.

    Article  CAS  PubMed  Google Scholar 

  57. Nakashima, T., Y. Kobayashi, S. Yamasaki, A. Kawakami, K. Eguchi, H. Sasaki, et al. 2000. Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappa B ligand: modulation of the expression by osteotropic factors and cytokines. Biochemical and Biophysical Research Communications 275: 768–775.

    Article  CAS  PubMed  Google Scholar 

  58. Clowes, J.A., B.L. Riggs, and S. Khosla. 2005. The role of the immune system in the pathophysiology of osteoporosis. Immunological Reviews 208: 207–27.

    Article  CAS  PubMed  Google Scholar 

  59. Riggs, B.L., S. Khosla, and L.J. Melton 3rd. 2002. Sex steroids and the construction and conservation of the adult skeleton. Endocrine Reviews 23: 279–302.

    Article  CAS  PubMed  Google Scholar 

  60. Zheng, S.X., Y. Vrindts, M. Lopez, D. De Groote, P.F. Zangerle, J. Collette, et al. 1997. Increase in cytokine production (IL-1Β beta, IL-6, TNF-Α-alpha but not IFN-gamma, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas 26: 63–71.

    Article  CAS  PubMed  Google Scholar 

  61. Pacifici, R., C. Brown, E. Puscheck, E. Friedrich, E. Slatopolsky, D. Maggio, et al. 1991. Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proceedings of the National Academy of Sciences of the United States of America 88: 5134–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Avitsur, R., J. Weidenfeld, and R. Yirmiya. 1999. Cytokines inhibit sexual behavior in female rats: II. Prostaglandins mediate the suppressive effects of interleukin-1beta. Brain, Behavior, and Immunity 13: 33–45.

    Article  CAS  PubMed  Google Scholar 

  63. LG HMR. 1999. Cytokines and prostaglandins. In: Aging Skeleton. San Diego: Academic Press

  64. Thomson, B.M., G.R. Mundy, and T.J. Chambers. 1987. Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption. Journal of Immunology 138: 775–9.

    CAS  Google Scholar 

  65. Kurihara, N., D. Bertolini, T. Suda, Y. Akiyama, and G.D. Roodman. 1990. IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1Β release. Journal of Immunology 144: 4226–30.

    CAS  Google Scholar 

  66. Das, U.N. 1991. Interaction(S) between essential fatty-acids, eicosanoids, cytokines, growth-factors and free-radicals—relevance to new therapeutic strategies in rheumatoid-arthritis and other collagen vascular diseases. Prostaglandins, Leukotrienes and Essential Fatty Acids 44: 201–210.

    Article  CAS  Google Scholar 

  67. Zhou, M.S., E.A. Jaimes, and L. Raij. 2004. Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats. American Journal of Hypertension 17: 167–171.

    Article  CAS  PubMed  Google Scholar 

  68. Mohler, E.R., L.C. Sorensen, J.K. Ghali, D.D. Schocken, P.W. Willis, J.A. Bowers, et al. 1997. Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Journal of the American College of Cardiology 30: 35–41.

    Article  CAS  PubMed  Google Scholar 

  69. Kataoka, C., K. Egashira, M. Ishibashi, S. Inoue, W.H. Ni, K. Hiasa, et al. 2004. Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis. American Journal of Physiology.Heart and Circulatory Physiology 286: H768–H774.

    Article  CAS  PubMed  Google Scholar 

  70. El-Bizri, N., G. Bkaily, S.M. Wang, D. Jacques, D. Regoli, P. D'Orleans-Juste, et al. 2003. Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells. Canadian Journal of Physiology and Pharmacology 81: 247–258.

    Article  CAS  PubMed  Google Scholar 

  71. Vajja, B.N.L., S. Juluri, M. Kumari, L. Kole, R. Chakrabarti, and V.D. Joshi. 2004. Lipopolysaccharide-induced paw edema model for detection of cytokine modulating anti-inflammatory agents. International Immunopharmacology 4: 901–909.

    Article  CAS  PubMed  Google Scholar 

  72. Halici, Z., B. Borekci, Y. Ozdemir, E. Cadirci, and H. Suleyman. 2008. Protective effects of amlodipine and lacidipine on ovariectomy-induced bone loss in rats. European Journal of Pharmacology 579: 241–245.

    Article  CAS  PubMed  Google Scholar 

  73. Kouoh, F., B. Gressier, T. Dine, M. Luyckx, C. Brunet, L. Ballester, et al. 2002. Antioxidant effects and anti-elastase activity of the calcium antagonist nicardipine on activated human and rabbit neutrophils—a potential antiatherosclerotic property of calcium antagonists? Cardiovascular Drugs and Therapy 16: 515–20.

    Article  CAS  PubMed  Google Scholar 

  74. Fansa, I., M. Gol, V. Nisanoglu, S. Yavas, Z. Iscan, and O. Tasdemir. 2003. Does diltiazem inhibit the inflammatory response in cardiopulmonary bypass? Medical Science Monitor 9: PI30–6.

    CAS  PubMed  Google Scholar 

  75. Komori, T., H. Yagi, S. Nomura, A. Yamaguchi, K. Sasaki, K. Deguchi, et al. 1997. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89: 755–764.

    Article  CAS  PubMed  Google Scholar 

  76. Ratti, C., E. Vulcano, G. Canton, M. Marano, L. Murena, and P. Cherubino. 2013. Factors affecting bone strength other than osteoporosis. Aging Clinical and Experimental Research 25: S9–S11.

    Article  PubMed  Google Scholar 

  77. Zhang, L.Q., H. Liu, and X.F. Huang. 2014. Relation of JAGGED 1 and collagen type 1 alpha 1 polymorphisms with bone mineral density in Chinese postmenopausal women. International Journal of Clinical Experimental Pathology 7: 7142–7147.

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Kimura, A., H. Inose, F. Yano, K. Fujita, T. Ikeda, S. Sato, et al. 2010. Runx1 and Runx2 cooperate during sternal morphogenesis. Development 137: 1159–1167.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Wang, Y.J., R.M. Belflower, Y.F. Dong, E.M. Schwarz, R.J. O'Keefe, and H. Drissi. 2005. Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis. Journal of Bone and Mineral Research 20: 1624–1636.

    Article  CAS  PubMed  Google Scholar 

  80. Ziros, P.G., T. Georgakopoulos, L. Habeos, E.K. Basdra, and A.G. Papavassiliou. 2004. Growth hormone attenuates the transcriptional activity of Runx2 by facilitating its physical association with Stat3 beta. Journal of Bone and Mineral Research 19: 1892–1904.

    Article  CAS  PubMed  Google Scholar 

  81. Kido, H.W., P.S. Bossini, C.R. Tim, N.A. Parizotto, A.F. da Cunha, I. Malavazi, et al. 2014. Evaluation of the bone healing process in an experimental tibial bone defect model in ovariectomized rats. Aging Clinical and Experimental Research 26: 473–481.

    Article  PubMed  Google Scholar 

  82. Franceschi, R.T., and G.Z. Xiao. 2003. Regulation of the osteoblast-specific transcription factor, runx2: responsiveness to multiple signal transduction pathways. Journal of Cellular Biochemistry 88: 446–454.

    Article  CAS  PubMed  Google Scholar 

  83. Kern, B., J.H. Shen, M. Starbuck, and G. Karsenty. 2001. Cbfa1 contributes to the osteoblast-specific expression of type I collagen genes. Journal of Biological Chemistry 276: 7101–7107.

    Article  CAS  PubMed  Google Scholar 

  84. Wojtowicz, A.M., K.L. Templeman, D.W. Hutmacher, R.E. Guldberg, and A.J. Garcia. 2010. Runx2 overexpression in bone marrow stromal cells accelerates bone formation in critical-sized femoral defects. Tissue Engineering Part A 16: 2795–2808.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Zhao, Z., Z. Wang, C. Ge, P. Krebsbach, and R.T. Franceschi. 2007. Healing cranial defects with AdRunx2-transduced marrow stromal cells. Journal of Dental Research 86: 1207–1211.

    Article  CAS  PubMed  Google Scholar 

  86. Chuang, L.S.H., K. Ito, and Y. Ito. 2013. RUNX family: regulation and diversification of roles through interacting proteins. International Journal of Cancer 132: 1260–1271.

    Article  CAS  Google Scholar 

  87. Otto, F., A.P. Thornell, T. Crompton, A. Denzel, K.C. Gilmour, I.R. Rosewell, et al. 1997. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89: 765–771.

    Article  CAS  PubMed  Google Scholar 

  88. Carbonare, L.D., M.T. Valenti, M. Zanatta, L. Donatelli, and Cascio V. Lo. 2009. Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Arthritis and Rheumatism 60: 3356–3365.

    Article  Google Scholar 

  89. Mann, V., E.E. Hobson, B.H. Li, T.L. Stewart, S.F.A. Grant, S.P. Robins, et al. 2001. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. Journal of Clinical Investigation 107: 899–907.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Kuivaniemi, H., G. Tromp, and D.J. Prockop. 1991. Mutations in collagen genes—causes of rare and some common diseases in humans. FASEB Journal 5: 2052–2060.

    CAS  PubMed  Google Scholar 

  91. Singh, M., P. Singh, S. Singh, P.K. Juneja, and T. Kaur. 2013. A haplotype derived from the common variants at the -1997G/T and Sp1 binding site of the COL1A1 gene influences risk of postmenopausal osteoporosis in India. Rheumatology International 33: 501–506.

    Article  CAS  PubMed  Google Scholar 

  92. Kurt-Sirin, O., H. Yilmaz-Aydogan, M. Uyar, M.F. Seyhan, T. Isbir, and A. Can. 2014. Combined effects of collagen type I alpha1 (COL1A1) Sp1 polymorphism and osteoporosis risk factors on bone mineral density in Turkish postmenopausal women. Gene 540: 226–31.

    Article  CAS  PubMed  Google Scholar 

  93. Orosa, B., P. Martinez, A. Gonzalez, D. Guede, J.R. Caeiro, J.J. Gomez-Reino, et al. 2015. Effect of lysophosphatidic acid receptor inhibition on bone changes in ovariectomized mice. Journal of Bone and Mineral Metabolism 33: 383–91.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This article supported by TUBİTAK, project number 112S044, and Ataturk University Scientific Experimental Project Office, project number 2011/017.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum, Turkey

    Emre Karakus

  2. Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    Zekai Halici, Abdulmecit Albayrak & Elif Cadirci

  3. Department of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey

    Yasin Bayir

  4. Department of Pathology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    Elif Demirci

  5. Department of Orthopedics and Traumatology, Ataturk University Faculty of Medicine, Erzurum, Turkey

    Ali Aydin

  6. Department of Pharmacology, Faculty of Pharmacy, Ibrahim Cecen University, Agrı, Turkey

    Berna Ozturk-Karagoz

  7. Department of Nuclear Medicine, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    Arif Kursat Ayan & Ali Sahin

  8. Department of Histology and Embryology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    Deniz Unal

Authors
  1. Emre Karakus
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  2. Zekai Halici
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  3. Abdulmecit Albayrak
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  4. Yasin Bayir
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  5. Elif Demirci
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  6. Ali Aydin
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  7. Berna Ozturk-Karagoz
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  8. Elif Cadirci
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  9. Arif Kursat Ayan
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  10. Ali Sahin
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  11. Deniz Unal
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Corresponding author

Correspondence to Emre Karakus.

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Karakus, E., Halici, Z., Albayrak, A. et al. Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat. Inflammation 39, 336–346 (2016). https://doi.org/10.1007/s10753-015-0254-6

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  • DOI: https://doi.org/10.1007/s10753-015-0254-6

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