Osteogenic protein and its peptide derivatives

  • Mahboobeh Nazari
  • Arash Minai-Tehrani
  • Rahman Emamzadeh
  • Mohammad Reza Nourani
Keywords: Bone morphogenetic proteins (BMP), tissue engineering, peptide


The role of tissue engineering in the field of bone regeneration has been one of the most studied topics in the past half century. To this end, the development of new biocompatible materials and scaffolds can be considered as an essential research purpose. Recently more attention has been focused on using bone morphogenetic proteins (BMPs). Current advances in the development of compatible derivatives of BMP motivated us to summarize them. This review focuses on several classes of short peptide sequences derived from BMP, and highlights in vitro and in vivo studies that demonstrate the potential of these materials as novel candidates for bone generation engineering and repair.


1.Przybylowski, C., et al., MC3T3 preosteoblast differentiation on bone morphogenetic protein-2 peptide ormosils. Journal of Materials Chemistry, 2012. 22(21): p. 10672-10683.
2.He, C., W. Nie, and W. Feng, Engineering of biomimetic nanofibrous matrices for drug delivery and tissue engineering. Journal of Materials Chemistry B, 2014. 2(45): p. 7828-7848.
3.Cho, H.-j., et al., Effective immobilization of BMP-2 mediated by polydopamine coating on biodegradable nanofibers for enhanced in vivo bone formation. ACS applied materials & interfaces, 2014. 6(14): p. 11225-11235.
4.Su, Y., et al., Controlled release of bone morphogenetic protein 2 and dexamethasone loaded in core–shell PLLACL–collagen fibers for use in bone tissue engineering. Acta biomaterialia, 2012. 8(2): p. 763-771.
5.Tautzenberger, A., A. Kovtun, and A. Ignatius, Nanoparticles and their potential for application in bone. International journal of nanomedicine, 2012. 7: p. 4545.
6.Kempen, D.H., et al., Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering. Biomaterials, 2008. 29(22): p. 3245-3252.
7.Kim, H.K., et al., Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7. Biomaterials, 2012. 33(29): p. 7057-7063.
8.David, L., J.-J. Feige, and S. Bailly, Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine & growth factor reviews, 2009. 20(3): p. 203-212.
9.Yasko, A.W., et al., The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. JBJS, 1992. 74(5): p. 659-670.
10.Shimer, A.L., F.C. Öner, and A.R. Vaccaro, Spinal reconstruction and bone morphogenetic proteins: open questions. Injury, 2009. 40: p. S32-S38.
11.Chung, Y.-I., et al., Enhanced bone regeneration with BMP-2 loaded functional nanoparticle–hydrogel complex. Journal of Controlled Release, 2007. 121(1): p. 91-99.
12.Chen, F.-m., et al., Release of bioactive BMP from dextran-derived microspheres: a novel delivery concept. International journal of pharmaceutics, 2006. 307(1): p. 23-32.
13.Xie, G., et al., Hydroxyapatite nanoparticles as a controlled-release carrier of BMP-2: absorption and release kinetics in vitro. Journal of Materials Science: Materials in Medicine, 2010. 21(6): p. 1875-1880.
14.Neumann, A., et al., BMP2-loaded nanoporous silica nanoparticles promote osteogenic differentiation of human mesenchymal stem cells. RSC Advances, 2013. 3(46): p. 24222-24230.
15.Gan, Q., et al., A dual-delivery system of pH-responsive chitosan-functionalized mesoporous silica nanoparticles bearing BMP-2 and dexamethasone for enhanced bone regeneration. Journal of Materials Chemistry B, 2015. 3(10): p. 2056-2066.
16.Sun, Y., et al., Peptide decorated nano-hydroxyapatite with enhanced bioactivity and osteogenic differentiation via polydopamine coating. Colloids and Surfaces B: Biointerfaces, 2013. 111: p. 107-116.
17.Kim, Y., J.N. Renner, and J.C. Liu, Incorporating the BMP-2 peptide in genetically-engineered biomaterials accelerates osteogenic differentiation. Biomaterials Science, 2014. 2(8): p. 1110-1119.
18.Saito, A., et al., Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2003. 1651(1): p. 60-67.
19.Saito, A., et al., Prolonged ectopic calcification induced by BMP‐2–derived synthetic peptide. Journal of Biomedical Materials Research Part A, 2004. 70(1): p. 115-121.
20.He, X., J. Ma, and E. Jabbari, Effect of grafting RGD and BMP-2 protein-derived peptides to a hydrogel substrate on osteogenic differentiation of marrow stromal cells. Langmuir, 2008. 24(21): p. 12508-12516.
21.Saito, A., et al., Repair of 20‐mm long rabbit radial bone defects using BMP‐derived peptide combined with an α‐tricalcium phosphate scaffold. Journal of Biomedical Materials Research Part A, 2006. 77(4): p. 700-706.
22.Lu, Y., et al., Coating with a modular bone morphogenetic peptide promotes healing of a bone-implant gap in an ovine model. PloS one, 2012. 7(11): p. e50378.
23.He, C., X. Jin, and P.X. Ma, Calcium phosphate deposition rate, structure and osteoconductivity on electrospun poly (L-lactic acid) matrix using electrodeposition or simulated body fluid incubation. Acta biomaterialia, 2014. 10(1): p. 419-427.
24.Zhou, X., et al., BMP-2 derived peptide and dexamethasone incorporated mesoporous silica nanoparticles for enhanced osteogenic differentiation of bone mesenchymal stem cells. ACS applied materials & interfaces, 2015. 7(29): p. 15777-15789.
25.An, H.S., et al., Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine, 2005. 30(1): p. 25-31.
26.Chubinskaya, S., M. Hurtig, and D.C. Rueger, OP-1/BMP-7 in cartilage repair. International orthopaedics, 2007. 31(6): p. 773-781.
27.Chaofeng, W., et al., Nucleus pulposus cells expressing hBMP7 can prevent the degeneration of allogenic IVD in a canine transplantation model. Journal of Orthopaedic Research, 2013. 31(9): p. 1366-1373.
28.Chen, Y. and T.J. Webster, Increased osteoblast functions in the presence of BMP‐7 short peptides for nanostructured biomaterial applications. Journal of Biomedical Materials Research Part A, 2009. 91(1): p. 296-304.
29.Tao, H., et al., BMP7-based functionalized self-assembling peptides for nucleus pulposus tissue engineering. ACS applied materials & interfaces, 2015. 7(31): p. 17076-17087.
30.Zhang, S., X. Zhao, and L. Spirio, PuraMatrix: self-assembling peptide nanofiber scaffolds. Scaffolding in tissue engineering, 2005: p. 217-238.
31.Kim, H.K., et al., Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation from multipotent bone marrow stromal cells and bone formation. Experimental & molecular medicine, 2017. 49(5): p. e328.
32.Choi, Y.J., et al., The identification of a heparin binding domain peptide from bone morphogenetic protein-4 and its role on osteogenesis. Biomaterials, 2010. 31(28): p. 7226-7238.
33.Zhang, X., et al., The role of NELL-1, a growth factor associated with craniosynostosis, in promoting bone regeneration. Journal of dental research, 2010. 89(9): p. 865-878.
34.Ting, K., et al., Human NELL‐1 expressed in unilateral coronal synostosis. Journal of Bone and Mineral Research, 1999. 14(1): p. 80-89.
35.Bokui, N., et al., Involvement of MAPK signaling molecules and Runx2 in the NELL1‐induced osteoblastic differentiation. FEBS letters, 2008. 582(2): p. 365-371.
36.Hasebe, A., et al., Efficient production and characterization of recombinant human NELL1 protein in human embryonic kidney 293-F cells. Molecular biotechnology, 2012. 51(1): p. 58-66.
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