Skip to main content
SpringerLink
Log in

Synthetic osteogenic growth peptide promotes differentiation of human bone marrow mesenchymal stem cells to osteoblasts via RhoA/ROCK pathway

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide that has attracted considerable clinical interest as a bone anabolic agent and hematopoietic stimulator. In vitro studies have demonstrated that OGP directly regulates the bone marrow mesenchymal stem cells’ (BMSCs) differentiation into osteoblasts. However, the exact mechanism of this process remains unknown. In the present study, we investigated the role of RhoA/ROCK signaling in differentiation along this lineage using human BMSCs. OGP treatment increased the mRNA level of bone morphogenetic protein-2 and alkaline phosphatase activity after osteogenic induction. Analysis of BMSCs induced in the presence of OGP revealed an increase in RhoA activity, and phosphorylation of FAK and cofilin. The ROCK-specific inhibitors, Y27632, blocked the OGP-induced regulation of BMSC differentiation. Taken together, these data suggest that OGP not only acts on BMSCs to stimulate osteogenic differentiation, but also in a dose-dependent manner, and this effect is mediated via the activation of RhoA/ROCK pathway.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Park JS, Yang HN, Jeon SY, Woo DG, Na K, Park KH (2010) Osteogenic differentiation of human mesenchymal stem cells using RGD-modified BMP-2 coated microspheres. Biomaterials 31(24):6239–6248

    Article  PubMed  CAS  Google Scholar 

  2. Lozano D, Manzano M, Doadrio JC, Salinas AJ, Vallet-Regi M, Gomez-Barrena E, Esbrit P (2010) Osteostatin-loaded bioceramics stimulate osteoblastic growth and differentiation. Acta Biomater 6(3):797–803

    Article  PubMed  CAS  Google Scholar 

  3. Kong L, Liu CJ (2008) Mediation of chondrogenic and osteogenic differentiation by an interferon-inducible p202 protein. Cell Mol Life Sci 65:3494–3506

    Article  PubMed  CAS  Google Scholar 

  4. Mattii L, Battolla B, Moscato S, Fazzi R, Galimberti S, Bernardini N, Dolfi A et al (2008) The small peptide OGP(10–14) acts through Src kinases and RhoA pathways in Mo-7e cells: morphologic and immunologic evaluation. Med Sci Monit 14:BR103–BR108

    PubMed  Google Scholar 

  5. Hamada K, Hirose M, Yamashita T, Ohgushi H (2008) Spatial distribution of mineralized bone matrix produced by marrow mesenchymal stem cells in self-assembling peptide hydrogel scaffold. J Biomed Mater Res A 84:128–136

    PubMed  Google Scholar 

  6. Hui Z, Yu L, Xiaoli Y, Xiang H, Fan Z, Ningbo H, Zhigang Y et al (2007) C-terminal pentapeptide of osteogenic growth peptide regulates hematopoiesis in early stage. J Cell Biochem 101:1423–1429

    Article  PubMed  Google Scholar 

  7. Bergeron E, Marquis ME, Chretien I, Faucheux N (2007) Differentiation of preosteoblasts using a delivery system with BMPs and bioactive glass microspheres. J Mater Sci Mater Med 18:255–263

    Article  PubMed  CAS  Google Scholar 

  8. Xu L, Liang X, Huang J, Dong Q, Xia L, Hu J, Zhang QH et al (2006) Osteogenic growth peptide regulates proliferation and differentiation of calvarial osteoblast-like cells of rat. Sichuan Da Xue Xue Bao Yi Xue Ban 37:445–448

    PubMed  CAS  Google Scholar 

  9. Yeh LC, Zavala MC, Lee JC (2006) C-type natriuretic peptide enhances osteogenic protein-1-induced osteoblastic cell differentiation via Smad5 phosphorylation. J Cell Biochem 97:494–500

    Article  PubMed  CAS  Google Scholar 

  10. Kim TJ, Seong J, Ouyang M, Sun J, Lu S, Hong JP, Wang N et al (2009) Substrate rigidity regulates Ca2+ oscillation via RhoA pathway in stem cells. J Cell Physiol 218:285–293

    Article  PubMed  CAS  Google Scholar 

  11. Pacary E, Tixier E, Coulet F, Roussel S, Petit E, Bernaudin M (2007) Crosstalk between HIF-1 and ROCK pathways in neuronal differentiation of mesenchymal stem cells, neurospheres and in PC12 neurite outgrowth. Mol Cell Neurosci 35:409–423

    Article  PubMed  CAS  Google Scholar 

  12. Ball SG, Shuttleworth CA, Kielty CM (2007) Platelet-derived growth factor receptor-alpha is a key determinant of smooth muscle alpha-actin filaments in bone marrow-derived mesenchymal stem cells. Int J Biochem Cell Biol 39:379–391

    Article  PubMed  CAS  Google Scholar 

  13. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6:483–495

    Article  PubMed  CAS  Google Scholar 

  14. Tsuda H, Wada T, Ito Y, Uchida H, Dehari H, Nakamura K, Sasaki K et al (2003) Efficient BMP2 gene transfer and bone formation of mesenchymal stem cells by a fiber-mutant adenoviral vector. Mol Ther 7:354–365

    Article  PubMed  CAS  Google Scholar 

  15. Yang XB, Roach HI, Clarke NM, Howdle SM, Quirk R, Shakesheff KM, Oreffo RO (2001) Human osteoprogenitor growth and differentiation on synthetic biodegradable structures after surface modification. Bone 29:523–531

    Article  PubMed  CAS  Google Scholar 

  16. Orui H, Imaizumi S, Ogino T, Motoyama T (2000) Effects of bone morphogenetic protein-2 on human tumor cell growth and differentiation: a preliminary report. J Orthop Sci 5:600–604

    Article  PubMed  CAS  Google Scholar 

  17. Obata A, Kasuga T (2009) Stimulation of human mesenchymal stem cells and osteoblasts activities in vitro on silicon-releasable scaffolds. J Biomed Mater Res A 91:11–17

    PubMed  Google Scholar 

  18. Docheva D, Padula D, Popov C, Mutschler W, Clausen-Schaumann H, Schieker M (2008) Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy. J Cell Mol Med 12:537–552

    Article  PubMed  Google Scholar 

  19. Chen ZX, Chang M, Peng YL, Zhao L, Zhan YR, Wang LJ, Wang R (2007) Osteogenic growth peptide C-terminal pentapeptide [OGP(10–14)] acts on rat bone marrow mesenchymal stem cells to promote differentiation to osteoblasts and to inhibit differentiation to adipocytes. Regul Pept 142:16–23

    Article  PubMed  CAS  Google Scholar 

  20. Jung Y, Song J, Shiozawa Y, Wang J, Wang Z, Williams B, Havens A et al (2008) Hematopoietic stem cells regulate mesenchymal stromal cell induction into osteoblasts thereby participating in the formation of the stem cell niche. Stem Cells 26:2042–2051

    Article  PubMed  Google Scholar 

  21. Lomri A, Lemonnier J, Delannoy P, Marie PJ (2001) Increased expression of protein kinase Calpha, interleukin-1alpha, and RhoA guanosine 5’-triphosphatase in osteoblasts expressing the Ser252Trp fibroblast growth factor 2 receptor Apert mutation: identification by analysis of complementary DNA microarray. J Bone Miner Res 16:705–712

    Article  PubMed  CAS  Google Scholar 

  22. Minamitani C, Otsuka T, Takai S, Matsushima-Nishiwaki R, Adachi S, Hanai Y, Mizutani J et al (2009) Involvement of Rho-kinase in sphingosine 1-phosphate-stimulated HSP27 induction in osteoblasts. Int J Mol Med 24:77–82

    PubMed  CAS  Google Scholar 

  23. Kuno M, Takai S, Matsushima-Nishiwaki R, Minamitani C, Mizutani J, Otsuka T, Harada A et al (2009) Rho-kinase inhibitors decrease TGF-beta-stimulated VEGF synthesis through stress-activated protein kinase/c-Jun N-terminal kinase in osteoblasts. Biochem Pharmacol 77:196–203

    PubMed  CAS  Google Scholar 

  24. Minamitani C, Otsuka T, Takai S, Matsushima-Nishiwaki R, Adachi S, Hanai Y, Mizutani J et al (2008) Involvement of Rho-kinase in prostaglandin F2alpha-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts. Mol Cell Endocrinol 291:27–32

    Article  PubMed  CAS  Google Scholar 

  25. Tokuda H, Hanai Y, Matsushima-Nishiwaki R, Yamauchi J, Doi T, Harada A, Takai S et al (2007) Rho-kinase regulates endothelin-1-stimulated IL-6 synthesis via p38 MAP kinase in osteoblasts. Biochem Biophys Res Commun 362:799–804

    Article  PubMed  CAS  Google Scholar 

  26. Vanella L, Kim DH, Asprinio D, Peterson SJ, Barbagallo I, Vanella A, Goldstein D (2010) HO-1 expression increases mesenchymal stem cell-derived osteoblasts but decreases adipocyte lineage. Bone 46(1):236–243

    Article  PubMed  CAS  Google Scholar 

  27. Kumarasuriyar A, Grondahl L, Nurcombe V, Cool SM (2009) Osteoblasts up-regulate the expression of extracellular proteases following attachment to Poly (beta-hydroxybutyrate-co-beta-hydroxyvalerate). Gene 428:53–58

    Article  PubMed  CAS  Google Scholar 

  28. Henderson JS, Johnson RB (1995) The effects of smokeless tobacco extract on bone nodule formation and mineralization by chick osteoblasts in vitro. Arch Oral Biol 40:615–621

    Article  PubMed  CAS  Google Scholar 

  29. Mattii L, Fazzi R, Moscato S, Segnani C, Pacini S, Galimberti S, D’Alessandro D et al (2004) Carboxy-terminal fragment of osteogenic growth peptide regulates myeloid differentiation through RhoA. J Cell Biochem 93:1231–1241

    Article  PubMed  CAS  Google Scholar 

  30. Elabd C, Basillais A, Beaupied H, Breuil V, Wagner N, Scheideler M, Zaragosi LE et al (2008) Oxytocin controls differentiation of human mesenchymal stem cells and reverses osteoporosis. Stem Cells 26:2399–2407

    Article  PubMed  CAS  Google Scholar 

  31. Pignolo RJ, Suda RK, McMillan EA, Shen J, Lee SH, Choi Y, Wright AC et al (2008) Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis. Aging Cell 7:23–31

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedics Surgery, Shanghai Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China

    Zixian Chen, Xiaofeng Wang, Yunchao Shao, Deyuan Shi, Tongyi Chen & Xiaoxing Jiang

  2. Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Sciences, Shanghai, 200031, China

    Dafu Cui

Authors
  1. Zixian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaofeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yunchao Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deyuan Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tongyi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dafu Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaoxing Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoxing Jiang.

Additional information

Zixian Chen and Xiaofeng Wang contributed equally to this experiment.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, Z., Wang, X., Shao, Y. et al. Synthetic osteogenic growth peptide promotes differentiation of human bone marrow mesenchymal stem cells to osteoblasts via RhoA/ROCK pathway. Mol Cell Biochem 358, 221–227 (2011). https://doi.org/10.1007/s11010-011-0938-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-0938-7

Keywords

Search

Navigation