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Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro

  • Original article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine.

Methods

The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor-beta 1 (TGF-β1) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed.

Results

MSCs when treated with either Shh or TGF-β1 showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems.

Conclusions

These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.

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References

  1. MF Pittenger AM Mackay SC Beck RK Jaiswal R Douglas JD Mosca et al. (1999) ArticleTitleMultilineage potential of adult human mesenchymal stem cells Science 284 143–7 10.1126/science.284.5411.143 Occurrence Handle10.1126/science.284.5411.143 Occurrence Handle1:CAS:528:DyaK1MXitlCnu7o%3D Occurrence Handle10102814

    Article  CAS  PubMed  Google Scholar 

  2. LC Murtaugh JH Chyung AB Lassar (1999) ArticleTitleSonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling Genes Dev 15 225–37 Occurrence Handle10.1101/gad.13.2.225

    Article  Google Scholar 

  3. S Kawai T Sugiura (2001) ArticleTitleCharacterization of human bone morphogenetic protein (BMP)-4 and -7 gene promoters: activation of BMP promoters by GLI, a sonic hedgehog mediator Bone (NY) 29 54–61 Occurrence Handle1:CAS:528:DC%2BD3MXltlOisrg%3D

    CAS  Google Scholar 

  4. M Enomoto-Iwamoto T Nakamura T Aikawa Y Higuchi T Yuasa A Yamaguchi et al. (2000) ArticleTitleHedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation J Bone Miner Res 15 1659–68 10.1359/jbmr.2000.15.9.1659 Occurrence Handle10.1359/jbmr.2000.15.9.1659 Occurrence Handle1:CAS:528:DC%2BD3cXmsF2mt7o%3D Occurrence Handle10976986

    Article  CAS  PubMed  Google Scholar 

  5. DB Pateder RN Rosier EM Schwarz PR Reynolds JE Puzas M D’Souza et al. (2000) ArticleTitlePTHrP expression in chondrocytes, regulation by TGF-β, and interactions between epiphyseal and growth plate chondrocytes Exp Cell Res 256 555–62 10.1006/excr.2000.4860 Occurrence Handle10.1006/excr.2000.4860 Occurrence Handle1:CAS:528:DC%2BD3cXisFelu7o%3D Occurrence Handle10772827

    Article  CAS  PubMed  Google Scholar 

  6. B Johnstone TM Hering AI Caplan VM Goldberg JU Yoo (1998) ArticleTitleIn vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells Exp Cell Res 238 265–72 10.1006/excr.1997.3858 Occurrence Handle10.1006/excr.1997.3858 Occurrence Handle1:CAS:528:DyaK1cXmt1SgtA%3D%3D Occurrence Handle9457080

    Article  CAS  PubMed  Google Scholar 

  7. CA Arévalo-Silva Y Cao Y Weng M Vacanti A Rodriguez CA Vacanti et al. (2001) ArticleTitleThe effect of fibroblast growth factor and transforming growth factor-β on porcine chondrocytes and tissue-engineered autologous elastic cartilage Tissue Eng 7 81–8 10.1089/107632700300003314 Occurrence Handle10.1089/107632700300003314 Occurrence Handle11224926

    Article  PubMed  Google Scholar 

  8. AA Worster AJ Nixon BD Brower-Toland J Williams (2000) ArticleTitleEffect of transforming growth factor β1 on chondrogenic differentiation of cultured equine mesenchymal stem cells Am J Vet Res 61 1003–10 10.2460/ajvr.2000.61.1003 Occurrence Handle10.2460/ajvr.2000.61.1003 Occurrence Handle1:CAS:528:DC%2BD3cXmvVSlt74%3D Occurrence Handle10976727

    Article  CAS  PubMed  Google Scholar 

  9. JL Graycar DA Miller BA Arrick RM Lyons HL Moses R Derynck (1989) ArticleTitleHuman transforming growth factor-β3: recombinant expression, purification, and biological activities in comparison with transforming growth factors-β1 and -β2 Mol Endocrinol 12 1977–86 10.1210/mend-3-12-1977 Occurrence Handle10.1210/mend-3-12-1977

    Article  Google Scholar 

  10. J Taipale PA Beachy (2001) ArticleTitleThe Hedgehog and Wnt signaling pathways in cancer Nature (Lond) 411 349–54 10.1038/35077219 Occurrence Handle10.1038/35077219 Occurrence Handle1:CAS:528:DC%2BD3MXktVSjsrw%3D

    Article  CAS  Google Scholar 

  11. S Hopyan N Gokgoz R Poon RC Gensure C Yu WG Cole et al. (2002) ArticleTitleA mutant PTH/PTHrP type 1 receptor in enchondromatosis Nat Genet 30 306–10 10.1038/ng844 Occurrence Handle10.1038/ng844 Occurrence Handle11850620

    Article  PubMed  Google Scholar 

  12. E Steck K Benz H Lorenz M Loew T Gress W Richter (2001) ArticleTitleChondrocyte expressed protein-68 (CEP-68), a novel human marker gene for cultured chondrocytes Biochem J 353 169–74 10.1042/0264-6021:3530169 Occurrence Handle10.1042/0264-6021:3530169 Occurrence Handle1:CAS:528:DC%2BD3MXotFWgsg%3D%3D Occurrence Handle11139377

    Article  CAS  PubMed  Google Scholar 

  13. FR Taylor D Wen EA Garber AN Carmillo DP Baker RM Arduini et al. (2001) ArticleTitleEnhanced potency of human Sonic hedgehog by hydrophobic modification Biochemistry 40 4359–71 10.1021/bi002487u Occurrence Handle10.1021/bi002487u Occurrence Handle1:CAS:528:DC%2BD3MXhvVSms74%3D Occurrence Handle11284692

    Article  CAS  PubMed  Google Scholar 

  14. I Sekiya JT Vuoristo BL Larson DJ Prockop (2000) ArticleTitleIn vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis Proc Natl Acad Sci USA 99 4397–402 10.1073/pnas.052716199 Occurrence Handle10.1073/pnas.052716199

    Article  Google Scholar 

  15. D Bosnakovski M Mizuno G Kim T Ishiguro M Okumura T Iwanaga et al. (2004) ArticleTitleChondrogenic differentiation of bovine bone marrow mesenchymal stem cells in pellet cultural system Exp Hematol 32 502–9 10.1016/j.exphem.2004.02.009 Occurrence Handle10.1016/j.exphem.2004.02.009 Occurrence Handle1:CAS:528:DC%2BD2cXktVCqt7g%3D Occurrence Handle15145219

    Article  CAS  PubMed  Google Scholar 

  16. L Weiser M Bhargava E Attia PA Torzilli (1999) ArticleTitleEffect of serum and platelet-derived growth factor on chondrocytes grown in collagen gels Tissue Eng 5 533–44 Occurrence Handle10.1089/ten.1999.5.533 Occurrence Handle1:CAS:528:DC%2BD3cXit1Oitw%3D%3D Occurrence Handle10611545

    Article  CAS  PubMed  Google Scholar 

  17. K Kellner K Lang A Papdimitriou U Leser S Milz MB Schulz et al. (2002) ArticleTitleEffects of hedgehog proteins on tissue engineering of cartilage in vitro Tissue Eng 8 561–72 10.1089/107632702760240481 Occurrence Handle10.1089/107632702760240481 Occurrence Handle1:CAS:528:DC%2BD38XmvVehtLs%3D Occurrence Handle12201996

    Article  CAS  PubMed  Google Scholar 

  18. V Lefebvre W Huang VR Harley PN Goodfellow B de Crombrugghe (1997) ArticleTitleSOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha I(II) collagen gene Mol Cell Biol 17 2336–46 Occurrence Handle1:CAS:528:DyaK2sXhvFOhsLg%3D Occurrence Handle9121483

    CAS  PubMed  Google Scholar 

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Warzecha, J., Göttig, S., Brüning, C. et al. Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. J Orthop Sci 11, 491–496 (2006). https://doi.org/10.1007/s00776-006-1058-1

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  • DOI: https://doi.org/10.1007/s00776-006-1058-1

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