Abstract
Secreted protein, acidic, cysteine-rich (SPARC)-related modular calcium binding 1 (SMOC1) has been implicated in the regulation of osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs). In this study, we found that a peptide (16 amino acids in length), which is located in the extracellular calcium (EC) binding domain of SMOC1, stimulated osteogenic differentiation of human BMSCs in vitro and calvarial bone regeneration in vivo. Treatment of BMSCs with SMOC1-EC peptide significantly stimulated their mineralization in a dose-dependent manner without changing their rate of proliferation. The expression of osteogenic differentiation marker genes, including type 1 collagen and osteocalcin, also increased in a dose-dependent manner. To examine the effect of the SMOC1-EC peptide on bone formation in vivo, the peptide was covalently immobilized onto hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) particles. X-ray photoelectron spectroscopy analysis showed that the peptide was successfully immobilized onto the surface of HA/β-TCP. Implantation of the SMOC1-EC peptide-immobilized HA/β-TCP particles into mouse calvarial defects and subsequent analyses using microcomputed tomography and histology showed significant bone regeneration compared with that of calvarial defects implanted with unmodified HA/β-TCP particles. Collectively, our data suggest that a peptide derived from the EC domain of SMOC1 induces osteogenic differentiation of human BMSCs in vitro and efficiently enhances bone regeneration in vivo.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Kitts DD, Weiler K. Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery. Curr Pharm Des 2003;9:1309–1323.
Sarmadi BH, Ismail A. Antioxidative peptides from food proteins: a review. Peptides 2010;31:1949–1956.
Rajanbabu V, Chen JY. Applications of antimicrobial peptides from fish and perspectives for the future. Peptides 2011;32:415–420.
Erdmann K, Cheung BW, Schröder H. The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease. J Nutr Biochem 2008;19:643–654.
Wang HX, Ng TB. Natural products with hypoglycemic, hypotensive, hypocholesterolemic, antiatherosclerotic and antithrombotic activities. Life Sci 1999;65:2663–2677.
Gauthier SA, Hewes RS. Transcriptional regulation of neuropeptide and peptide hormone expression by the Drosophila dimmed and cryptocephal genes. J Exp Biol 2006;209(Pt 10):1803–1815.
Kim HK, Kim JH, Park DS, Park KS, Kang SS, Lee JS, et al. Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7. Biomaterials 2012;33:7057–7063.
Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med 2008;2:1–13.
Shields LB, Raque GH, Glassman SD, Campbell M, Vitaz T, Harpring J, et al. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine (Phila Pa 1976) 2006;31:542–547.
Toth JM, Boden SD, Burkus JK, Badura JM, Peckham SM, McKay WF. Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment. Spine (Phila Pa 1976) 2009;34:539–550.
Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering. Biomaterials 2003;24:4353–4364.
Paderni S, Terzi S, Amendola L. Major bone defect treatment with an osteoconductive bone substitute. Chir Organi Mov 2009;93:89–96.
Hench LL, Polak JM. Third-generation biomedical materials. Science 2002;295:1014–1017.
Acharya B, Chun SY, Kim SY, Moon C, Shin HI, Park EK. Surface immobilization of MEPE peptide onto HA/β-TCP ceramic particles enhances bone regeneration and remodeling. J Biomed Mater Res B Appl Biomater 2012;100:841–849.
Chun SY, Acharya B, Shin HI, Park EK. RGD Immobilized human demineralized dentin particles for bone autografting. Tissue Eng Regen Med 2010;7:69–75.
Choi YA, Lim J, Kim KM, Acharya B, Cho JY, Bae YC, et al. Secretome analysis of human BMSCs and identification of SMOC1 as an important ECM protein in osteoblast differentiation. J Proteome Res 2010;9:2946–2956.
Vannahme C, Smyth N, Miosge N, Gösling S, Frie C, Paulsson M, et al. Characterization of SMOC-1, a novel modular calcium-binding protein in basement membranes. J Biol Chem 2002;277:37977–37986.
Chen ZY, Zhang JL, Yao HX, Wang PY, Zhu J, Wang W, et al. Aberrant methylation of the SPARC gene promoter and its clinical implication in gastric cancer. Sci Rep 2014;4:7035.
Dreieicher E, Beck KF, Lazaroski S, Boosen M, Tsalastra-Greul W, Beck M, et al. Nitric oxide inhibits glomerular TGF-beta signaling via SMOC-1. J Am Soc Nephrol 2009;20:1963–1974.
Okada I, Hamanoue H, Terada K, Tohma T, Megarbane A, Chouery E, et al. SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet 2011;88:30–41.
Vannahme C, Gösling S, Paulsson M, Maurer P, Hartmann U. Characterization of SMOC-2, a modular extracellular calcium-binding protein. Biochem J 2003;373(Pt 3):805–814.
Lee SY, Lim J, Khang G, Son Y, Choung PH, Kang SS, et al. Enhanced ex vivo expansion of human adipose tissue-derived mesenchymal stromal cells by fibroblast growth factor-2 and dexamethasone. Tissue Eng Part A 2009;15:2491–2499.
Park EK, Lee YE, Choi JY, Oh SH, Shin HI, Kim KH, et al. Cellular biocompatibility and stimulatory effects of calcium metaphosphate on osteoblastic differentiation of human bone marrow-derived stromal cells. Biomaterials 2004;25:3403–3411.
Kim JA, Shon YH, Lim JO, Yoo JJ, Shin HI, Park EK. MYOD mediates skeletal myogenic differentiation of human amniotic fluid stem cells and regeneration of muscle injury. Stem Cell Res Ther 2013;4:147.
Häfeli UO, Pauer GJ, Unnithan J, Prayson RA. Fibrin glue system for adjuvant brachytherapy of brain tumors with 188Re and 186Re-labeled microspheres. Eur J Pharm Biopharm 2007;65:282–288.
Lee JY, Choi YS, Lee SJ, Chung CP, Park YJ. Bioactive peptide-modified biomaterials for bone regeneration. Curr Pharm Des 2011;17:2663–2676.
Fan VH, Tamama K, Au A, Littrell R, Richardson LB, Wright JW, et al. Tethered epidermal growth factor provides a survival advantage to mesenchymal stem cells. Stem Cells 2007;25:1241–1251.
Chen WS, Lazar CS, Lund KA, Welsh JB, Chang CP, Walton GM, et al. Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation. Cell 1989;59:33–43.
Wiley HS. Trafficking of the ErbB receptors and its influence on signaling. Exp Cell Res 2003;284:78–88.
Choi YA, Shin HI, Park EK. Effect of SMOC1-derived peptide on osteoblast differentiation of human bone narrow mesenchymal stem cells. Korean J Oral Maxillofac Pathol 2014;38:29–34.
Klemencic M, Novinec M, Maier S, Hartmann U, Lenarcic B. The heparin-binding activity of secreted modular calcium-binding protein 1 (SMOC-1) modulates its cell adhesion properties. PLoS One 2013;8: e56839.
Aroca-Aguilar JD, Sánchez-Sánchez F, Ghosh S, Fernández-Navarro A, Coca-Prados M, Escribano J. Interaction of recombinant myocilin with the matricellular protein SPARC: functional implications. Invest Ophthalmol Vis Sci 2011;52:179–189.
Kwon HS, Johnson TV, Tomarev SI. Myocilin stimulates osteogenic differentiation of mesenchymal stem cells through mitogen-activated protein kinase signaling. J Biol Chem 2013;288:16882–16894.
Durrieu MC, Pallu S, Guillemot F, Bareille R, Amédée J, Baquey CH, et al. Grafting RGD containing peptides onto hydroxyapatite to promote osteoblastic cells adhesion. J Mater Sci Mater Med 2004;15:779–786.
Tessmar JK, Mikos AG, Göpferich A. Amine-reactive biodegradable diblock copolymers. Biomacromolecules 2002;3:194–200.
Wang V, Misra G, Amsden B. Immobilization of a bone and cartilage stimulating peptide to a synthetic bone graft. J Mater Sci Mater Med 2008;19:2145–2155.
Maier S, Paulsson M, Hartmann U. The widely expressed extracellular matrix protein SMOC-2 promotes keratinocyte attachment and migration. Exp Cell Res 2008;314:2477–2487.
Marie PJ. Targeting integrins to promote bone formation and repair. Nat Rev Endocrinol 2013;9:288–295.
Author information
Authors and Affiliations
Corresponding author
Additional information
These authors contributed equally to this work.
Rights and permissions
About this article
Cite this article
Kim, J.A., Choi, YA., Yun, HS. et al. Extracellular calcium-binding peptide-modified ceramics stimulate regeneration of calvarial bone defects. Tissue Eng Regen Med 13, 57–65 (2016). https://doi.org/10.1007/s13770-015-9066-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13770-015-9066-x