The Role of Chondrogenic Factors in Differentiation of Bone Marrow Stromal Cells to the Cartilage Lineage

  • Emily M. Florine
  • Alan J. Grodzinsky
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 7)


Bone marrow stromal cells (BMSCs) are an established cell choice for cartilage repair because they are easily harvested, expanded, and differentiated into a cartilage phenotype characterized by aggrecan and type II collagen production. Transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), and Dexamethasone (Dex) all influence the process of chondrogenesis. Although difficult challenges remain for optimizing the use of BMSCs for cartilage tissue engineering, in vitro culture systems present an excellent opportunity for studying chondrogenesis and understanding how progenitor cells respond to their biological, chemical, and mechanical microenvironment.


Bone Marrow Stromal Cell Cartilage Repair Autologous Chondrocyte Implantation Proteoglycan Synthesis Cartilage Tissue Engineering 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Barry F, Boynton RE, Liu B, Murphy JM (2001) Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res 268:189–200PubMedCrossRefGoogle Scholar
  2. Byers BA, Mauck RL, Chiang IE, Tuan RS (2008) Transient exposure to transforming growth factor beta 3 under serum-free conditions enhances the biomechanical and biochemical maturation of tissue-engineered cartilage. Tissue Eng Part A 14:1821–1834PubMedCentralPubMedCrossRefGoogle Scholar
  3. Chen FH, Tuan RS (2008) Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther 10:223PubMedCentralPubMedCrossRefGoogle Scholar
  4. Derfoul A, Perkins GL, Hall DJ, Tuan RS (2006) Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes. Stem Cells 24:1487–1495PubMedCrossRefGoogle Scholar
  5. Dickhut A, Pelttari K, Janicki P, Wagner W, Eckstein V, Egermann M, Richter W (2009) Calcification or dedifferentiation: requirement to lock mesenchymal stem cells in a desired differentiation stage. J Cell Physiol 219:219–226PubMedCrossRefGoogle Scholar
  6. Fan H, Hu Y, Qin L, Li X, Wu H, Lv R (2006) Porous gelatin-chondroitin-hyaluronate tri-copolymer scaffold containing microspheres loaded with TGF-β1 induces differentiation of mesenchymal stem cells in vivo for enhancing cartilage repair. J Biomed Mater Res A 77:785–794PubMedCrossRefGoogle Scholar
  7. Fan J, Varshney RR, Ren L, Cai D, Wang DA (2009) Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng Part B Rev 15:75–86PubMedCrossRefGoogle Scholar
  8. Florine EM, Vanderploeg EJ, Kopesky PW, Miller RE, Grodzinsky AJ (2010) Dexamethasone suppresses aggrecan catabolism in BMSC-seeded peptide hydrogels. In: 56th Transactions of the Orthopaedic Research Society, New Orleans 1326Google Scholar
  9. Getgood A, Brooks R, Fortier L, Rushton N (2009) Articular cartilage tissue engineering: today’s research, tomorrow’s practice? J Bone Joint Surg Br 91:565–576PubMedCrossRefGoogle Scholar
  10. Goldring MB, Tsuchimochi K, Ijiri K (2006) The control of chondrogenesis. J Cell Biochem 97:33–44PubMedCrossRefGoogle Scholar
  11. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238:265–272PubMedCrossRefGoogle Scholar
  12. Kisiday JD, Kopesky PW, Evans CH, Grodzinsky AJ, McIlwraith CW, Frisbie DD (2008) Evaluation of adult equine bone marrow- and adipose-derived progenitor cell chondrogenesis in hydrogel cultures. J Orthop Res 26:322–331PubMedCrossRefGoogle Scholar
  13. Kopesky PW, Vanderploeg EJ, Sandy JS, Kurz B, Grodzinsky AJ (2010) Self-assembling peptide hydrogels modulate in vitro chondrogenesis of bovine bone marrow stromal cells. Tissue Eng Part A 16:465–477PubMedCentralPubMedCrossRefGoogle Scholar
  14. Kopesky PW, Vanderploeg EJ, Kisiday JD, Frisbie DD, Sandy JD, Grodzinsky AJ (2011) Controlled delivery of transforming growth factor β1 by self-assembling peptide hydrogels induces chondrogenesis of bone marrow stromal cells and modulates Smad2/3 signaling. Tissue Eng Part A 17:83–92PubMedCentralPubMedCrossRefGoogle Scholar
  15. Kotlarz H, Gunnarsson CL, Fang H, Rizzo JA (2009) Insurer and out-of-pocket costs of osteoarthritis in the US: evidence from national survey data. Arthritis Rheum 60:3546–3553PubMedCrossRefGoogle Scholar
  16. Martel-Pelletier J, Di Battista JA, Lajeunesse D, Pelletier JP (1998) IGF/IGFBP axis in cartilage and bone in osteoarthritis pathogenesis. Inflamm Res 47:90–100PubMedCrossRefGoogle Scholar
  17. Mi Z, Ghivizzani SC, Lechman E, Glorioso JC, Evans CH, Robbins PD (2003) Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees. Arthritis Res Ther 5:R132–R139PubMedCentralPubMedCrossRefGoogle Scholar
  18. Miller RE, Grodzinsky AJ, Vanderploeg EJ, Lee C, Ferris DJ, Barrett MF, Kisiday JD, Frisbie DD (2010a) Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair. Osteoarthritis Cartilage 18:1608–1619PubMedCentralPubMedCrossRefGoogle Scholar
  19. Miller RE, Grodzinsky AJ, Cummings K, Plaas AH, Cole AA, Lee RT, Patwari P (2010b) Intraarticular injection of heparin-binding insulin-like growth factor 1 sustains delivery of insulin-like growth factor 1 to cartilage through binding to chondroitin sulfate. Arthritis Rheum 62:3686–3694PubMedCentralPubMedCrossRefGoogle Scholar
  20. Mouw JK, Connelly JT, Wilson CG, Michael KE, Levenston ME (2007) Dynamic compression regulates the expression and synthesis of chondrocyte-specific matrix molecules in bone marrow stromal cells. Stem Cells 25:655–663PubMedGoogle Scholar
  21. Newton R, Holden NS (2007) Separating transrepression and transactivation: a distressing divorce for the glucocorticoid receptor? Mol Pharmacol 72:799–809PubMedCrossRefGoogle Scholar
  22. Nixon AJ, Fortier LA, Williams J, Mohammed H (1999) Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites. J Orthop Res 17:475–487PubMedCrossRefGoogle Scholar
  23. Noth U, Steinert AF, Tuan RS (2008) Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol 4:371–380PubMedGoogle Scholar
  24. Palmer GD, Steinert A, Pascher A, Gouze E, Gouze JN, Betz O, Johnstone B, Evans CH, Ghivizzani SC (2005) Gene-induced chondrogenesis of primary mesenchymal stem cells in vitro. Mol Ther 12:219–228PubMedCrossRefGoogle Scholar
  25. Park JS, Na K, Woo DG, Yang HN, Park KH (2009) Determination of dual delivery for stem cell differentiation using dexamethasone and TGF-ß3 in/on polymeric microspheres. Biomaterials 30:4796–4805PubMedCrossRefGoogle Scholar
  26. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  27. Prockop DJ (2009) Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Mol Ther 17:939–946PubMedCentralPubMedCrossRefGoogle Scholar
  28. Schmidt MB, Chen EH, Lynch SE (2006) A review of the effects of insulin-like growth factor and platelet-derived growth factor on in vivo cartilage healing and repair. Osteoarthritis Cartilage 14:403–412PubMedCrossRefGoogle Scholar
  29. Shah RN, Shah NA, Del Rosario Lim MM, Hsieh C, Nuber G, Stupp SI (2010) Supramolecular design of self-assembling nanofibers for cartilage regeneration. Proc Natl Acad Sci USA 107:3293–3298PubMedCentralPubMedCrossRefGoogle Scholar
  30. Shi Y, Massague J (2003) Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113:685–700PubMedCrossRefGoogle Scholar
  31. Starkman BG, Cravero JD, Delcarlo M, Loeser RF (2005) IGF-1 stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK. Biochem J 389:723–729PubMedCentralPubMedGoogle Scholar
  32. Tokunou T, Miller R, Patwari P, Davis ME, Segers VF, Grodzinsky AJ, Lee RT (2008) Engineering insulin-like growth factor-1 for local delivery. FASEB J 22:1886–1893PubMedCentralPubMedCrossRefGoogle Scholar
  33. Tuli R, Tuli S, Nandi S, Huang X, Manner PA, Hozack WJ, Danielson KG, Hall DJ, Tuan RS (2003) Transforming growth factor-β-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk. J Biol Chem 278:41227–41236PubMedCrossRefGoogle Scholar
  34. van der Kraan PM, van den Berg WB (2000) Anabolic and destructive mediators in osteoarthritis. Curr Opin Clin Nutr Metab Care 3:205–211PubMedCrossRefGoogle Scholar
  35. 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-1 in a three-dimensional matrix. J Orthop Res 19:738–749PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Center for Biomedical EngineeringMassachusetts Institute of TechnologyCambridgeUSA

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