Skip to main content
SpringerLink
Log in

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

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

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.

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

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5
Figure 6

Similar content being viewed by others

References

  • 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 89:1235–1249

    Article  CAS  PubMed  Google Scholar 

  • 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 8:73–84

    Article  CAS  PubMed  Google Scholar 

  • 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 7:143–152

    Article  Google Scholar 

  • 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):2183–2188

  • Brzoska M, Geiger H, Gauer S, Baer P (2005) Epithelial differentiation of human adipose tissue-derived adult stem cells. Biochem Biophys Res Commun 330:142–150

    Article  CAS  PubMed  Google Scholar 

  • 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 343:644–652

    Article  CAS  PubMed  Google Scholar 

  • 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 11:20130784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 174:101–109

    Article  PubMed  Google Scholar 

  • 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 269:25–33

    Article  CAS  PubMed  Google Scholar 

  • Denko CW, Boja B, Moskowitz RW (1990) Growth promoting peptides in osteoarthritis: insulin, insulin-like growth factor-1, growth hormone. J Rheumatol 17:1217–1221

    CAS  PubMed  Google Scholar 

  • Derynck R, Zhang YE (2003) Smad-dependent and smad-independent pathways in TGF-beta family signalling. Nature 425:577–584

    Article  CAS  PubMed  Google Scholar 

  • 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 84:276–288

    Article  CAS  Google Scholar 

  • 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 11:55–64

    Article  CAS  PubMed  Google Scholar 

  • 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 20:1271–1284

    Article  CAS  Google Scholar 

  • 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 199:117–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hendriks J, Riesle J, van Blitterswijk CA (2007) Co-culture in cartilage tissue engineering. J Tissue Eng Regen Med 1:170–178

    Article  CAS  PubMed  Google Scholar 

  • 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 211:682–691

    Article  CAS  PubMed  Google Scholar 

  • 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 320:914–919

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Im GI (2009) Chondrogenic differentiation of adipose tissue-derived mesenchymal stem cells: greater doses of growth factor are necessary. J Orthop Res 27:612–619

    Article  PubMed  Google Scholar 

  • 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 207:267–274

    Article  CAS  PubMed  Google Scholar 

  • 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 227:2003–2012

    Article  CAS  PubMed  Google Scholar 

  • 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 9:929–939

    Article  CAS  PubMed  Google Scholar 

  • 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 21:626–636

    Article  CAS  PubMed  Google Scholar 

  • 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 13:1621–1630

    Article  CAS  PubMed  Google Scholar 

  • 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 25:229–247

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martel-Pelletier J, Di BJA, Lajeunesse D, Pelletier JP (1998) IGF/IGFBP axis in cartilage and bone in osteoarthritis pathogenesis. Inflamm Res 47:90–100

    Article  CAS  PubMed  Google Scholar 

  • 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 20:1575–1588

    Article  PubMed  Google Scholar 

  • 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 51:440–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 71:382–391

    Article  CAS  PubMed  Google Scholar 

  • 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 16:531–541

    Article  CAS  PubMed  Google Scholar 

  • 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 278:36563–36571

    Article  CAS  PubMed  Google Scholar 

  • 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 81:1096–1103

    CAS  PubMed  Google Scholar 

  • 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 115:1091–1105

    Article  CAS  PubMed  Google Scholar 

  • 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 183:55–61

    Article  CAS  PubMed  Google Scholar 

  • 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 32:274–280

    Article  CAS  PubMed  Google Scholar 

  • 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:e84206

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 103:98–100

    Article  CAS  PubMed  Google Scholar 

  • 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 19:738–749

    Article  CAS  PubMed  Google Scholar 

  • 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 37:937–943

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 13:4279–4295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Author notes

    Authors and Affiliations

    1. Department of Orthopaedics, Huai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second Hospital, No. 62 Huaihai Road South, Huai’an, 223002, China

      Quan Zhou, Jiali Zhao, Wei Pan, Jin Xu & Sumei Chen

    2. Department of Joint Surgery, Second People’s Hospital of Hunan Province, Changsha, 410007, China

      Baojun Li

    Authors
    1. Quan Zhou
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Baojun Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Jiali Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Wei Pan
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Jin Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Sumei Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Sumei Chen.

    Additional information

    Editor: Tetsuji Okamoto

    Quan Zhou and Baojun Li contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zhou, Q., Li, B., Zhao, J. et al. IGF-I induces adipose derived mesenchymal cell chondrogenic differentiation in vitro and enhances chondrogenesis in vivo. In Vitro Cell.Dev.Biol.-Animal 52, 356–364 (2016). https://doi.org/10.1007/s11626-015-9969-9

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11626-015-9969-9

    Keywords

    Search

    Navigation