期刊论文详细信息
BMC Musculoskeletal Disorders
The effects of zoledronate on the survival and function of human osteoblast-like cells
Tien-Yu Yang2  Po-Yao Chuang2  Chin-Chang Cheng3  Kuo-Chin Huang1 
[1] Present address: No. 6, West Section, Chia-Pu Road, Pu-Tz City Chiayi County 61313, Taiwan;Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan;Chang Gung University College of Medicine, Taoyuan, Taiwan
关键词: Bone repair;    Bone regeneration;    Osteoblast;    Bisphosphonates;    Zoledronate;   
Others  :  1233990
DOI  :  10.1186/s12891-015-0818-5
 received in 2015-08-20, accepted in 2015-11-13,  发布年份 2015
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【 摘 要 】

Background

Prolonged bisphosphonate treatment might suppress bone remodeling to the extent that normal bone repair is impaired. While this adverse side effect is usually ascribed to the negative effects of bisphosphonates on osteoclast survival and function, these effects on osteoblasts are still unclear.

Methods

In the current study, we hypothesized that zoledronate (ZOL) at the μM level might present negative effects on osteoblast survival and function. In vitro analyses of proliferation, migration and differentiation were performed on human osteoblast-like cells.

Results

Our results revealed that ZOL treatment dose- and time-dependently induced apoptosis of osteoblasts after concentrations had reached 10 μM (p < 0.001). The concentrations at which ZOL inhibited osteoblast migration by 50 % were between 10 and 15 μM. Moreover, there was a dose-dependent reduction in the extent of matrix mineralization, but without a concomitant inhibition of osteogenic differentiation in terms of secreted type I collagen and osteocalcin and of alkaline phosphatase activity per viable cell. Analyses of the expression of osteogenic genes confirmed that ZOL at the μM level had no effects on osteogenic differentiation of osteoblasts.

Conclusion

We concluded that ZOL at the μM level affected osteoblast survival and migration, but did not affect differentiation. The pathophysiological implications of ZOL at the μM level on skeletal disorders need to be investigated and clarified in the future researches.

【 授权许可】

   
2015 Huang et al.

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【 参考文献 】
  • [1]Russell RG. Bisphosphonates: mode of action and pharmacology. Pediatrics. 2007; 119:S150-S162.
  • [2]Coxon FP, Thompson K, Rogers MJ. Recent advances in understanding the mechanism of action of bisphosphonates. Curr Opin Pharmacol. 2006; 6:307-312.
  • [3]Rodan GA, Fleisch HA. Bisphosphonates: mechanism of action. J Clin Invest. 1996; 97:2692-2696.
  • [4]Jung A, Bisaz S, Fleisch H. The binding of pyrophosphate and two diphosphonates by hydroxyapatite crystals. Calcif Tissue Res. 1973; 11:269-280.
  • [5]van Beek E, Pieterman E, Cohen L, Löwik C, Papapoulos S. Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun. 1999; 264:108-111.
  • [6]Rousselle AV, Heymann D. Osteoclastic acidification pathways during bone resorption. Bone. 2002; 30:533-540.
  • [7]Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007; 357:1799-1809.
  • [8]Chesnutt CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004; 19:1241-1249.
  • [9]Duque G, Rivas D. Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. J Bone Miner Res. 2007; 22:1603-1611.
  • [10]Plotkin LI, Manolagas SC, Bellido T. Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblast/osteocytes with novel analogs. Bone. 2006; 39:443-452.
  • [11]Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, Whelan DB, Weiler PJ, Laupacis A. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011; 305:783-789.
  • [12]Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005; 90:1294-1301.
  • [13]Tobias JH, Chow JW, Chambers TJ. 3-Amino-1-hydroxypropylidine-1-bisphosphonate (AHPrBP) suppresses not only the induction of new, but also the persistence of existing bone-forming surfaces in rat cancellous bone. Bone. 1993; 14:619-623.
  • [14]Kozloff KM, Volakis LI, Marini JC, Caird MS. Near-infrared fluorescent probe traces bisphosphonate delivery and retention in vivo. J Bone Miner Res. 2010; 25:1748-1758.
  • [15]Otto S, Pautke C, Opelz C, Westphal I, Drosse I, Schwager J, Bauss F, Ehrenfeld M, Schieker M. Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism. J Oral Maxillofacial Surg. 2010; 68:2837-2845.
  • [16]Liberman UA. Long-term safety of bisphosphonate therapy for osteoporosis: a review of the evidence. Drugs Aging. 2006; 23:289-298.
  • [17]Ebert R, Zeck S, Krug R, Meissner-Weigl J, Schneider D, Seefried L, Eulert J, Jakob F. Pulse treatment with zoledronic acid causes sustained commitment of bone marrow derived mesenchymal stem cells for osteogenic differentiation. Bone. 2009; 44:858-864.
  • [18]Issack PS, Lauerman MH, Helfet DL, Doty SB, Lane JM. Alendronate inhibits PTH (1–34)-induced bone morphogenetic protein expression in MC3T3-E1 preosteoblastic cells. HSS J. 2007; 3:169-172.
  • [19]Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006; 38:617-627.
  • [20]Chapurlat RD, Delmas PD. Bone microdamage: a clinical perspective. Osteoporos Int. 2009; 20:1299-1308.
  • [21]Norman TL, Wang Z. Microdamage of human cortical bone: incidence and morphology in long bones. Bone. 1997; 20:375-379.
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