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IGF-I induces adipose derived mesenchymal cell chondrogenic differentiation in vitro and enhances chondrogenesis in vivo

  • Quan Zhou
  • Baojun Li
  • Jiali Zhao
  • Wei Pan
  • Jin Xu
  • Sumei ChenEmail author
Article

Abstract

Recent studies have demonstrated that insulin-like growth factor-1 (IGF-I) modulates bone mesenchymal stem cell chondrogenic differentiation independent of transforming growth factor beta (TGF-β) signaling in vitro. However, it is unclear whether IGF-I can solely modulate human adipose-derived mesenchymal cell (hAMC) chondrogenic differentiation, or whether it has additive effects with TGF-β1 to induce chondrogenic differentiation in vitro and development of mature cartilage in vivo. We investigated the effect of IGF-I on the induction of hAMC chondrogenic differentiation in the presence or absence of transforming growth factor beta 1 (TGF-β1) in vitro, and chondrogenesis of the induced hAMC in vivo. The results showed that IGF-I alone induced collagen type II, aggrecan, and Sox9 mRNA expression and collagen type II and aggrecan proteins expressions in hAMCs. Notably, there was greater mRNA expression of collagen type II, aggrecan and Sox9, and greater protein expression of collagen type II and aggrecan following TGF-β1 + IGF-I treatment, compared to either TGF-β1 or IGF-I-treated hAMCs. These results were confirmed in cartilage tissues derived from induced hAMCs. These findings indicate that IGF-I alone has the ability to induce chondrogenic differentiation and has additive effects with TGF-β1 to induce chondrogenic differentiation in vitro and in vivo.

Keywords

Chondrogenic differentiation Insulin-like growth factor Multipotentmesenchymal cells Tissue engineering 

Notes

Acknowledgments

This research was supported by grants from the scientific research fund of the Bureau of Public Health of Jiangsu province (no. H201254) and the Huai’an Technology Support Program (social development) funded projects (no. HAS2013046).

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Baddoo M, Hill K, Wilkinson R, Gaupp D, Hughes C, Kopen GC, Phinney DG (2003) Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. J Cell Biochem 89:1235–1249CrossRefPubMedGoogle Scholar
  2. Blunk T, Sieminski AL, Gooch KJ, Courter DL, Hollander AP, Nahir AM, Langer R, Vunjak-Novakovic G, Freed LE (2002) Differential effects of growth factors on tissue-engineered cartilage. Tissue Eng 8:73–84CrossRefPubMedGoogle Scholar
  3. Bogdanova-Jantniece A, Berzins U, Kozlovska T (2014) Growth properties and pluriopotency marker expression of spontaneously formed three-dimensional aggregates of human adipose-derived stem cells. Int J Stem Cells 7:143–152CrossRefGoogle Scholar
  4. Bonnevie ED, Puetzer JL, Bonassar LJ (2014) Enhanced boundary lubrication properties of engineered menisci by lubricin localization with insulin-like growth factor I treatment. J Biomech 47(9):2183–2188Google Scholar
  5. Brzoska M, Geiger H, Gauer S, Baer P (2005) Epithelial differentiation of human adipose tissue-derived adult stem cells. Biochem Biophys Res Commun 330:142–150CrossRefPubMedGoogle Scholar
  6. Chiou M, Xu Y, Longaker MT (2006) Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells. Biochem Biophys Res Commun 343:644–652CrossRefPubMedGoogle Scholar
  7. Correia SI, Pereira H, Silva-Correia J, Van Dijk CN, Espregueira-Mendes J, Oliveira JM, Reis RL (2014) Current concepts: tissue engineering and regenerative medicine applications in the ankle joint. J R Soc Interface 11:20130784CrossRefPubMedPubMedCentralGoogle Scholar
  8. De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, Dragoo JL, Ashjian P, Thomas B, Benhaim P, Chen I, Fraser J, Hedrick MH (2003) Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174:101–109CrossRefPubMedGoogle Scholar
  9. Deng Y, Cao H, Cu F, Xu D, Lei Y, Tan Y, Magdalou J, Wang H, Chen L (2013) Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats. Toxicol Appl Pharmacol 269:25–33CrossRefPubMedGoogle Scholar
  10. Denko CW, Boja B, Moskowitz RW (1990) Growth promoting peptides in osteoarthritis: insulin, insulin-like growth factor-1, growth hormone. J Rheumatol 17:1217–1221PubMedGoogle Scholar
  11. Derynck R, Zhang YE (2003) Smad-dependent and smad-independent pathways in TGF-beta family signalling. Nature 425:577–584CrossRefPubMedGoogle Scholar
  12. Fortier LA, Mohammed HO, Lust G, Nixon AJ (2002) Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Joint Surg Br Vol 84:276–288CrossRefGoogle Scholar
  13. Fukumoto T, Sperling JW, Sanyal A, Fitzsimmons JS, Reinholz GG, Conover CA, O’Driscoll SW (2003) Combined effects of insulin-like growth factor-1 and transforming growth factor-beta1 on periosteal mesenchymal cells during chondrogenesis in vitro. Osteoarthr Cartil 11:55–64CrossRefPubMedGoogle Scholar
  14. Gao S, Zhao P, Lin C, Sun Y, Wang Y, Zhou Z, Yang D, Wang X, Xu H, Zhou F, Cao L, Zhou W, Ning K, Chen X, Xu J (2014) Differentiation of human-adipose derived stem cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds. Tissue Eng A 20:1271–1284CrossRefGoogle Scholar
  15. Goude MC, McDevitt TC, Temenoff JS (2014) Chondroitin sulfate microparticles modulate transforming growth factor-β1-indcuced chondrogenesis of human mesenchymal stem cell spheroids. Cells Tissues Organs 199:117–130CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hendriks J, Riesle J, van Blitterswijk CA (2007) Co-culture in cartilage tissue engineering. J Tissue Eng Regen Med 1:170–178CrossRefPubMedGoogle Scholar
  17. Hennig T, Lorenz H, Thiel A, Goetzke K, Dickhut A, Geiger F, Richter W (2007) Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6. J Cell Physiol 211:682–691CrossRefPubMedGoogle Scholar
  18. Indrawattana N, Chen G, Tadokoro M, Shann LH, Ohgushi H, Tateishi T, Tanaka J, Bunyaratvej A (2004) Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochem Biophys Res Commun 320:914–919CrossRefPubMedGoogle Scholar
  19. Kim HJ, Im GI (2009) Chondrogenic differentiation of adipose tissue-derived mesenchymal stem cells: greater doses of growth factor are necessary. J Orthop Res 27:612–619CrossRefPubMedGoogle Scholar
  20. Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G (2007) Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp Neurol 207:267–274CrossRefPubMedGoogle Scholar
  21. Li J, Zhao Q, Wang E, Zhang C, Wang G, Yuan Q (2012) Dynamic compression of rabbit adipose-derived stem cells transfected with insulin-like growth factor 1 in chitosan/gelatin scaffolds induces chondrogenesis and matrix biosynthesis. J Cell Physiol 227:2003–2012CrossRefPubMedGoogle Scholar
  22. Lin Y, Luo E, Chen X, Liu L, Qiao J, Yan Z, Li Z, Tang W, Zheng X, Tian W (2005) Molecular and cellular characterization during chondrogenic differentiation of adipose tissue-derived stromal cells in vitro and cartilage formation in vivo. J Cell Mol Med 9:929–939CrossRefPubMedGoogle Scholar
  23. Longobardi L, O’Rear L, Aakula S, Johnstone B, Shimer K, Chytil A, Horton WA, Moses HL, Spagnoli A (2006) Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J Bone Miner Res 21:626–636CrossRefPubMedGoogle Scholar
  24. Madry H, Padera R, Seidel J, Langer R, Freed LE, Trippel SB, Vunjak-Novakovic G (2002) Gene transfer of a human insulin-like growth factor I cDNA enhances tissue engineering of cartilage. Hum Gene Ther 13:1621–1630CrossRefPubMedGoogle Scholar
  25. Madry H, Kaul G, Zurakowski D, Vunjak-Novakovic G, Cucchiarini M (2013) Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model. Eur Cell Mater 25:229–247PubMedPubMedCentralGoogle Scholar
  26. Martel-Pelletier J, Di BJA, Lajeunesse D, Pelletier JP (1998) IGF/IGFBP axis in cartilage and bone in osteoarthritis pathogenesis. Inflamm Res 47:90–100CrossRefPubMedGoogle Scholar
  27. Merceron C, Portron S, Masson M, Lesoeur J, Fellah BH, Gauthier O, Geffroy O, Weiss P, Guicheux J, Vinatier C (2011) The effect of two- and three-dimensional cell culture on the chondrogenic potential of human adipose-derived mesenchymal stem cells after subcutaneous transplantation with an injectable hydrogel. Cell Transplant 20:1575–1588CrossRefPubMedGoogle Scholar
  28. Middleton JF, Tyler JA (1992) Upregulation of insulin-like growth factor I gene expression in the lesions of osteoarthritic human articular cartilage. Ann Rheum Dis 51:440–447CrossRefPubMedPubMedCentralGoogle Scholar
  29. Milne M, Quail JM, Baran DT (1998) Dexamethasone stimulates osteogenic differentiation in vertebral and femoral bone marrow cell cultures: comparison of IGF-I gene expression. J Cell Biochem 71:382–391CrossRefPubMedGoogle Scholar
  30. Nixon AJ, Lillich JT, Burton-Wurster N, Lust G, Mohammed HO (1998) Differentiated cellular function in fetal chondrocytes cultured with insulin-like growth factor-I and transforming growth factor-beta. J Orthop Res 16:531–541CrossRefPubMedGoogle Scholar
  31. Oh CD, Chun JS (2003) Signaling mechanisms leading to the regulation of differentiation and apoptosis of articular chondrocytes by insulin-like growth factor-1. J Biol Chem 278:36563–36571CrossRefPubMedGoogle Scholar
  32. Olney RC, Tsuchiya K, Wilson DM, Mohtai M, Maloney WJ, Schurman DJ, Smith RL (1996) Chondrocytes from osteoarthritic cartilage have increased expression of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and -5, but not IGF-II or IGFBP-4. J Clin Endocrinol Metab 81:1096–1103PubMedGoogle Scholar
  33. Pelton RW, Saxena B, Jones M, Moses HL, Gold LI (1991) Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J Cell Biol 115:1091–1105CrossRefPubMedGoogle Scholar
  34. Sakimura K, Matsumoto T, Miyamoto C, Osaki M, Shindo H (2006) Effects of insulin-like growth factor I on transforming growth factor beta1 induced chondrogenesis of synovium-derived mesenchymal stem cells cultured in a polyglycolic acid scaffold. Cells Tissues Organs 183:55–61CrossRefPubMedGoogle Scholar
  35. Schouten JS, Van den Ouweland FA, Valkenburg HA, Lamberts SW (1993) Insulin-like growth factor-1: a prognostic factor of knee osteoarthritis. Br J Rheumatol 32:274–280CrossRefPubMedGoogle Scholar
  36. Sowa Y, Imura T, Numajiri T, Takeda K, Mabuchi Y, Matsuzaki Y, Nishino K (2013) Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest. PLoS One 8:e84206CrossRefPubMedPubMedCentralGoogle Scholar
  37. Takagi M, Umetsu Y, Fujiwara M, Wakitani S (2007) High inoculation cell density could accelerate the differentiation of human bone marrow mesenchymal stem cells to chondrocyte cells. J Biosci Bioeng 103:98–100CrossRefPubMedGoogle Scholar
  38. Worster AA, Brower-Toland BD, Fortier LA, Bent SJ, Williams J, Nixon AJ (2001) Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix. J Orthop Res 19:738–749CrossRefPubMedGoogle Scholar
  39. Yi C, Ma C, Xie Z, Zhang G, Song W, Zhou X, Cao Y (2013) Down-regulation of programmed cell death 5 by insulin-like growth factor 1 in osteoarthritis chondrocytes. Int Orthop 37:937–943CrossRefPubMedPubMedCentralGoogle Scholar
  40. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Society for In Vitro Biology 2016

Authors and Affiliations

  • Quan Zhou
    • 1
  • Baojun Li
    • 2
  • Jiali Zhao
    • 1
  • Wei Pan
    • 1
  • Jin Xu
    • 1
  • Sumei Chen
    • 1
    Email author
  1. 1.Department of OrthopaedicsHuai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second HospitalHuai’anChina
  2. 2.Department of Joint SurgerySecond People’s Hospital of Hunan ProvinceChangshaChina

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