Abstract
Erythropoietin (EPO) could promote the angiogenesis and may also play a role in bone regeneration. This study was conducted to evaluate the osteogenesis and angiogenesis effects of EPO and the efficacy of deproteinized bovine bone/recombinant human EPO scaffold on bone defect repair. Twenty-four healthy adult goats were chosen to build goat defects model and randomly divided into four groups. The goats were treated with DBB/rhEPO scaffolds (group A), porous DBB scaffolds (group B), autogenous cancellous bone graft (group C), and nothing (group D). Animals were evaluated with radiological and histological methods at 4, 8 and 12 weeks after surgery. The grey value of radiographs was used to evaluate the healing of the defects and the outcome revealed that the group A had a better outcome of defect healing compared with group B (P < 0.05). However, the grey values in group A were lower than group C at week 4 and week 8 (P < 0.05), but at week 12 their difference had no statistical significance (P > 0.05). The newly formed bone area was calculated from histological sections and the results demonstrated that the amount of new bone in group A increased significantly compared with that in group B (P < 0.05) but was inferior to that in group C (P > 0.05) at 4, 8, 12 weeks respectively. In addition, the expression of vascular endothelial growth factor (VEGF) by immunohistochemical testing and real-time polymerase chain reaction at 12 weeks in group A was significantly higher than that in group B (P < 0.05), and also better than that in group C at week 4 and week 8 (P < 0.05), but at week 12 their difference had no statistical significance (P > 0.05). Therefore, EPO has significant effects on bone formation and angiogenesis, and has capacity to promote the repair of bone defects. It is worthy of being recommended to further studies.
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References
Mao ZW, Shi HF, Guo R. Enhanced angiogenesis of porous collagen scaolds by incorporation of TMC/DNA complexes encoding vascular endothelial growth factor. Acta Biomater. 2009;5:2983–94.
Yu H, VandeVord PJ, Mao L. Improved tissue-engineered bone regeneration by endothelial cell mediated vascularization. Biomaterials. 2009;30:508–17.
Gorustovich AA, Roether JA, Boccaccini AR. Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Eng Part B Rev. 2010;16:199–207.
Kang P, Xie X, Tan Z, et al. Repairing defect and preventing collapse of femoral head in a steroid-induced osteonecrotic of femoral head animal model using strontium-doped calcium polyphosphate combined BM-MNCs. J Mater Sci Mater Med. 2015;26:80.
Zhang B, Xia L, Hu B, et al. Effects of recombinant human erythropoietin on angiogenesis in chronic ischemic porcine myocardium [J]. Zhonghua Wai Ke Za Zhi. 2014;52:366–9.
Li C, Shi C, Kim J, et al. Erythropoietin promotes bone formation through EphrinB2/EphB4 signaling. J Dent Res. 2015;94:455–63.
Teixeira M, Rodrigues-Santos P, Garrido P. Cardiac antiapoptotic and proproliferative effect of recombinant human erythropoietin in a moderate stage of chronic renal failure in the rat. J Pharm Bioallied Sci. 2012;4:76–83.
Choi D, Schroer SA, Lu SY. Erythropoietin protects against diabetes through direct effects on pancreatic beta cells. J Exp Med. 2010;207:2831–42.
Xiong M, Chen S, Yu H, Liu Z, Zeng Y, Li F. Neuroprotection of erythropoietin and methylprednisolone against spinal cord ischemia-reperfusion injury. J Huazhong Univ Sci Technol Med Sci. 2011;31:652–6.
Kakavas S, Demestiha T, Vasileiou P, Xanthos T. Erythropoetin as a novel agent with pleiotropic effects against acute lung injury. Eur J Clin Pharmacol. 2011;67:1–9.
Galeano M, Altavilla D, Bitto A. Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds. Crit Care Med. 2006;34:1139–46.
Rezaeian F, Wettstein R, Amon M. Erythropoiet in protects critically perfused flap tissue. Ann Surg. 2008;248:919–29.
Kim J, Jung Y, Sun H. Erythropoietin mediated bone formation is regulated by mTOR signaling. J Cell Biochem. 2012;113:220–8.
Holstein JH, Orth M, Scheuer C, et al. Erythropoietin stimulates bone formation, cell proliferation, and angiogenesis in a femoral segmental defect model in mice. Bone. 2011;49:1037–45.
Wan L, Zhang F, He Q, et al. EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis[J]. PLoS One. 2014;9:e102010.
Chen S, Li J, Peng H, Zhou J, Fang H. Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats. Int J Mol Med. 2014;33:840–8.
Li Q, Zhou G, Yu X, Wang T, Xi Y, Tang Z. Porous deproteinized bovine bone scaffold with three-dimensional localized drug delivery system using chitosan microspheres. Biomed Eng Online. 2015;14:33.
Wiltfang J, Jatschmann N, Hedderich J, Neukam FW, Schlegel KA, Gierloff M. Effect of deproteinized bovine bone matrix coverage on the resorption of iliac cortico-spongeous bone grafts-a prospective study of two cohorts. Clin Oral Implants Res. 2014;25:e127–32.
Yildirim M, Spiekermann H, Handt S, et al. Maxillary sinus augmentation with the xenograft Bio-Oss and autogenous intraoral bone for qualitative improvement of the implant site: a histologic and histomorphometric clinical study in humans. Int J Oral Maxillofac Implants. 2001;16:23–33.
Martinez A, Balboa O, Gasamans I, Otero-Cepeda XL, Guitian F. Deproteinated bovine bone vs. beta-tricalcium phosphate as bone graft substitutes: histomorphometric longitudinal study in the rabbit cranial vault. Clin Oral Implants Res. 2015;26:623–32.
Guo L, Luo T, Fang Y, et al. Effects of erythropoietin on osteoblast proliferation and function. Clin Exp Med. 2014;14:69–76.
Shiozawa Y, Jung Y, Ziegler AM, et al. Erythropoietin couples hematopoiesis with bone formation. PLoS One. 2010;5:10853.
Garcia P, Speidel V, Scheuer C. Low dose erythropoietin stimulates bone healing in mice. J Orthop Res. 2011;29:165–72.
Holstein JH, Menger MD, Scheuer C, et al. Erythropoietin (EPO): EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing. Life Sci. 2007;80:893–900.
Bakhshi H, Rasouli MR, Parvizi J. Can local Erythropoietin administration enhance bone regeneration in osteonecrosis of femoral head? Med Hypotheses. 2012;79:154–6.
Young S, Patel ZS, Kretlow JD. Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model. Tissue Eng Part A. 2009;15:2347–62.
Betsch M, Thelen S, Santak L, et al. The role of erythropoietin and bone marrow concentrate in the treatment of osteochondral defects in mini-pigs. PLoS One. 2014;9:e92766.
Hu R, Cheng Y, Jing H. Erythropoietin promotes the protective properties of transplanted endothelial progenitor cells against acute lung injury via PI3K/Akt pathway. Shock. 2014;42:327–36.
Du G, Zhu H, Yu P, et al. SMND-309 promotes angiogenesis in human umbilical vein endothelial cells through activating erythropoietin receptor/STAT3/VEGF pathways. Eur J Pharmacol. 2013;700:173–80.
Weibing Z, Wang L. Correlation between vascular endothelial growth factor temporal expression and new bone formation in midpalatal suture during rapid maxillary expansion. Hua Xi Kou Qiang Yi Xue Za Zhi. 2014;32:561–5.
Unger RE, Dohle E, Kirkpatrick CJ. Improving vascularization of engineered bone through the generation of pro-angiogenic effects in co-culture systems. Adv Drug Deliv Rev. 2015;94:116–25.
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This study was supported by the National Natural Science Fund of China (81271976/H0605 and 81171763).
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Donghai Li, Liqing Deng and Xiaowei Xie contributed equally to this work and should be regarded as first co-author.
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Li, D., Deng, L., Xie, X. et al. Evaluation of the osteogenesis and angiogenesis effects of erythropoietin and the efficacy of deproteinized bovine bone/recombinant human erythropoietin scaffold on bone defect repair. J Mater Sci: Mater Med 27, 101 (2016). https://doi.org/10.1007/s10856-016-5714-5
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DOI: https://doi.org/10.1007/s10856-016-5714-5