Skip to main content
SpringerLink
Log in

The effects on dermal wound healing using novel peptide modified by bone morphogenic protein-2

  • Original Article
  • Regenerative Medicine
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

An Erratum to this article was published on 10 November 2014

Abstract

New alternatives to growth factors, such as transforming growth factor beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF) and bone morphogenetic proteins (BMP), for wound healing have been devised and investigated to maintain their biological properties, as well as to reduce their complicated adverse effects. In this study, we have focused on OP10 peptide modified from BMPs which regulates a variety of cellular processes, such as proliferation, differentiation, bone/cartilage morphogenesis, apoptosis, and wound healing. The wound healing process involves multiple physiological processes, such as proliferation and migration of dermal fibroblasts and epidermal keratinocytes. These processes play an important role in collagen production and the regulation of elastin levels in dermal tissue regeneration. In order to evaluate the promotion of cell proliferation and migration using OP10, MTT and scratch assays were carried out using normal dermal human fibroblast (NHDF). OP10 promoted proliferation and migration of NHDFs similar to those found with FGF. OP10 was focused on this study and was further investigated for its wound skin regeneration capacity and compared to FGF, by mRNA and protein expression. OP10 was found to increase the protein expression of procollagen and the mRNA level of Type I collagen, to levels similar or even higher than that found with FGF. OP10 inhibits not only matrix metalloproteinase (MMP)-1 expression but also elastase secretion, higher than the effects seen with FGF. Based on these results, we conclude that OP10 plays a role in the regeneration of damaged skin by activating dermal fibroblasts in vitro and may have further potential as wound repair or cosmetic materials for wrinkle improvement.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. SE Lynch, JC Nixon, RB Colvin, et al., Role of plateletderived growth factor in wound healing: synergistic effects with other growth factors, Proc Natl Acad Sci U S A, 84, 7696 (1987).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. MA Loot, SB Kenter, FL Au, et al., Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls, Eur J Cell Biol, 81, 153 (2002).

    Article  PubMed  Google Scholar 

  3. L Attisano, JL Wrana, Signal transduction by the TGF-beta superfamily, Science, 296, 1646 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. H Chang, CW Brown, MM Matzuk, Genetic analysis of the mammalian transforming growth factor-beta superfamily, Endocr Rev, 23, 787 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. BL Hogan, Bone morphogenetic proteins in development, Curr Opin Genet Dev, 6, 432 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. DM Kingsley, The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms, Genes Dev, 8, 133 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. MR Urist, BS Strates, Bone morphogenetic protein, J Dent Res, 50, 1392 (1971).

    Article  CAS  PubMed  Google Scholar 

  8. J Moura, L da Silva, MT Cruz, et al., Molecular and cellular mechanisms of bone morphogenetic proteins and activins in the skin: potential benefits for wound healing, Arch Dermatol Res, 305, 557 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. VA Botchkarev, Bone morphogenetic proteins and their antagonists in skin and hair follicle biology, J Invest Dermatol, 120, 36 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. N Hirt-Burri, C Scaletta, S Gerber, et al., Wound-healing gene family expression differences between fetal and foreskin cells used for bioengineered skin substitutes, Artif Organs, 32, 509 (2008).

    Article  PubMed  Google Scholar 

  11. S Kaiser, P Schirmacher, A Philipp, et al., Induction of bone morphogenetic protein-6 in skin wounds. Delayed reepitheliazation and scar formation in BMP-6 overexpressing transgenic mice, J Invest Dermatol, 111, 1145 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. EA Hwang, HB Lee, KC Tark, Comparison of bone morphogenetic protein receptors expression in the fetal and adult skin, Yonsei Med J, 42, 581 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. M Blessing, P Schirmacher, S Kaiser, Overexpression of bone morphogenetic protein-6 (BMP-6) in the epidermis of transgenic mice: inhibition or stimulation of proliferation depending on the pattern of transgene expression and formation of psoriatic lesions, J Cell Biol, 135, 227 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. M Blessing, LB Nanney, LE King, et al., Chemical skin carcinogenesis is prevented in mice by the induced expression of a TGF-beta related transgene, Teratog Carcinog Mutagen, 15, 11 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. S Wach, P Schirmacher, M Protschka, et al., Overexpression of bone morphogenetic protein-6 (BMP-6) in murine epidermis suppresses skin tumor formation by induction of apoptosis and downregulation of fos/jun family members, Oncogene, 20, 7761 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. I Kurokawa, K Kusumoto, K Bessho, et al., Immunohistochemical expression of bone morphogenetic protein-2 in pilomatricoma, Br J Dermatol, 143, 754 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. JY Lee, JE Choo, YS Choi, et al., Assembly of collagen-binding peptide with collagen as a bioactive scaffold for osteogenesis in vitro and in vivo, Biomaterials, 28, 4257 (2007).

    Article  CAS  PubMed  Google Scholar 

  18. JJ Qian, RS Bhatnagar, Enhanced cell attachment to anorganic bone mineral in the presence of a synthetic peptide related to collagen, J Biomed Mater Res, 31, 545 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. KM Malinda, AB Wysocki, JE Koblinski, et al., Angiogenic laminin-derived peptides stimulate wound healing, Int J Biochem Cell Biol, 40, 2771 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. KP Krafts, Tissue repair: The hidden drama, Organogenesis, 6, 225 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  21. G Broughton, JE Janis, CE Attinger, The basic science of wound healing, Plast Reconstr Surg, 117, 12S (2006).

    Article  Google Scholar 

  22. SA Eming, T Krieg, JM Davidson, Inflammation in wound repair: molecular and cellular mechanisms, J Invest Dermatol, 127, 514 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. J Stiernberg, AM Norfleet, WR Redin, et al., Acceleration of full-thickness wound healing in normal rats by the synthetic thrombin peptide, TP508, Wound Repair Regen, 8, 204 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. MJ Oudhoff, KL Kroeze, K Nazmi, et al., Structure-activity analysis of histatin, a potent wound healing peptide from human saliva: cyclization of histatin potentiates molar activity 1,000-fold, FASEB J, 23, 3928 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. JM Smiell, TJ Wieman, DL Steed, et al., Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies, Wound Repair Regen, 7, 335 (1999).

    Article  CAS  PubMed  Google Scholar 

  26. T Velnar, T Bailey, V Smrkolj, The wound healing process: an overview of the cellular and molecular mechanisms, J Int Med Res, 37, 1528 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. JM Reinke, H Sorg, Wound repair and regeneration, Eur Surg Res, 49, 35 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. NT Bennett, GS Schultz, Growth factors and wound healing: biochemical properties of growth factors and their receptors, Am J Surg, 165, 728 (1993).

    Article  CAS  PubMed  Google Scholar 

  29. JW Madden, EE Peacock Jr., Studies on the biology of collagen during wound healing 3. Dynamic metabolism of scar collagen and remodeling of dermal wounds, Ann Surg, 174, 511 (1971).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. SP Bennett, GD Griffiths, AM Schor, et al., Growth factors in the treatment of diabetic foot ulcers, Br J Surg, 90, 133 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. AH Chang, MT Stephan, L Lisowski, et al., Erythroid-specific human factor IX delivery from in vivo selected hematopoietic stem cells following nonmyeloablative conditioning in hemophilia B mice, Mol Ther, 16, 1745 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. S Even-Ram, KM Yamada, Cell migration in 3D matrix, Curr Opin Cell Biol, 17, 524 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. T Sasaki, The effects of basic fibroblast growth factor and doxorubicin on cultured human skin fibroblasts: relevance to wound healing, J Dermatol, 19, 664 (1992).

    CAS  PubMed  Google Scholar 

  34. BM Hantash, L Zhao, JA Knowles, et al., Adult and fetal wound healing, Front Biosci, 13, 51 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. M van der Rest, R Garrone, Collagen family of proteins, FASEB J, 5, 2814 (1991).

    PubMed  Google Scholar 

  36. G Fitsialos, AA Chassot, L Turchi, et al., Transcriptional signature of epidermal keratinocytes subjected to in vitro scratch wounding reveals selective roles for ERK1/2, p38, and phosphatidylinositol 3-kinase signaling pathways, J Biol Chem, 282, 15090 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Y Satoh, D Saitoh, A Takeuchi, et al., ERK2 dependent signaling contributes to wound healing after a partial-thickness burn, Biochem Biophys Res Commun, 381, 118 (2009).

    Article  CAS  PubMed  Google Scholar 

  38. TA Khavari, J Rinn, Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia, Cell Cycle, 6, 2928 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. JD Raffetto, R Vasquez, DG Goodwin, et al., Mitogen-activated protein kinase pathway regulates cell proliferation in venous ulcer fibroblasts, Vasc Endovascular Surg, 40, 59 (2006).

    Article  PubMed  Google Scholar 

  40. RL Klemke, S Cai, AL Giannini, et al., Regulation of cell motility by mitogen-activated protein kinase, J Cell Biol, 137, 481 (1997).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. M Sumitra, P Manikandan, VS Gayathri, et al., Emblica officinalis exerts wound healing action through up-regulation of collagen and extracellular signal-regulated kinases (ERK1/2), Wound Repair Regen, 17, 99 (2009).

    Article  PubMed  Google Scholar 

  42. KR Cutroneo, Gene therapy for tissue regeneration, J Cell Biochem, 88, 418 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. J Varani, P Perone, SE Fligiel, et al., Inhibition of type I procollagen production in photodamage: correlation between presence of high molecular weight collagen fragments and reduced procollagen synthesis, J Invest Dermatol, 119, 122 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. M Madlener, WC Parks, S Werner, Matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) are differentially expressed during excisional skin wound repair, Exp Cell Res, 242, 201 (1998).

    Article  CAS  PubMed  Google Scholar 

  45. TT Meckmongkol, R Harmon, P McKeown-Longo, et al., The fibronectin synergy site modulates TGF-beta-dependent fibroblast contraction, Biochem Biophys Res Commun, 360, 709 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. M Wankell, B Munz, G Hubner, et al., Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis, EMBO J, 20, 5361 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Institute, Winnova Co., Ltd., Seoul, Republic of Korea

    Yoonjung Hong, Narae Choi & Bosun Kwon

  2. Research Institute, Wooridul Life Sciences Ltd., Seoul, Republic of Korea

    Hyeeun Shim, Sehee Kim & Bosun Kwon

  3. Neurosurgery, Seoul St. Mary’s Hospital of the Catholic University, Seoul, Republic of Korea

    Jinsung Kim

  4. Department of Life science, Ewha womans University, Seoul, Republic of Korea

    Jiwon Hwang

  5. Division of Periodontology, Department of Dentistry, School of Medicine, Republic of Inha University, Incheon, Republic of Korea

    Jeongho Yun

Authors
  1. Yoonjung Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyeeun Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sehee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Narae Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jinsung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiwon Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeongho Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bosun Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bosun Kwon.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hong, Y., Shim, H., Kim, S. et al. The effects on dermal wound healing using novel peptide modified by bone morphogenic protein-2. Tissue Eng Regen Med 11, 397–404 (2014). https://doi.org/10.1007/s13770-014-0037-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-014-0037-4

Key words

Search

Navigation