International Orthopaedics

, Volume 36, Issue 9, pp 1961–1966 | Cite as

Behaviour of human physeal chondro-progenitorcells in early growth plate injury response in vitro

  • Karin Pichler
  • Barbara Schmidt
  • Eva E. Fischerauer
  • Beate Rinner
  • Gottfried Dohr
  • Andreas Leithner
  • Annelie M. Weinberg
Original Paper



The aim of this study was to investigate the proliferation and differentiation behaviour of a defined cell population gained from the human growth plate, namely, chondro-progenitorcells (CPCs), in the initial inflammatory phase of growth plate injury response in vitro.


Growth plate cells were sorted via FACS and differentiated along adipogenic and osteogenic lineage to confirm their progenitor features. To mimic the inflammatory phase of injury response at the growth plate they were treated with IL-1β and exposed to cyclic mechanical loading. A BrdU assay was used to investigate CPC proliferation. CPC differentiation behaviour was analysed by RT-PCR.


CPCs (CD45-, CD34-, CD73+, CD90+, and CD105+) showed a successful differentiation along adipogenic and osteogenic lineage. Under conditions simulating the inflammatory phase of injury response at the growth plate in vitro CPCs differentiated towards hypertrophy while chondrogenesis and ossification were inhibited. Proliferation was not significantly altered.


This study showed that CPCs can be isolated from the human growth plate and expanded in vitro. In the first phase of injury response at the growth plate these cells differentiate towards hypertrophy. As longitudinal growth is obtained by chondrocyte proliferation and volume increase during hypertrophy this maturation might be the first step towards post-traumatic growth disorders such as unwanted premature ossification of the growth plate.


Growth Plate Injury Response Inflammatory Phase Bone Bridge Growth Plate Chondrocytes 
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.



The authors appreciate support from the Laura Bassi Center of Expertise BRIC (Bioresorbable Implants for Children; FFG -Austria). Furthermore they would like to acknowledge Rudolf Schmied for his valuable technical assistance. They declare no actual or potential conflict of interest.


  1. 1.
    Olsen BR, Reginato AM, Wang W (2000) Bone development. Annu Rev Cell Dev Biol 16:191–220PubMedCrossRefGoogle Scholar
  2. 2.
    Wattenbarger JM, Gruber HE, Phieffer LS (2002) Physeal fractures, part I: histologic features of bone, cartilage, and bar formation in a small animal model. J Pediatr Orthop 22(6):703–709PubMedCrossRefGoogle Scholar
  3. 3.
    Shapiro F (1987) Epiphyseal disorders. N Engl J Med 317(27):1702–1710PubMedCrossRefGoogle Scholar
  4. 4.
    Chung R, Foster BK, Xian CJ (2011) Injury responses and repair mechanisms of the injured growth plate. Front Biosci (Schol Ed) 3:117–125CrossRefGoogle Scholar
  5. 5.
    Zhou FH, Foster BK, Sander G, Xian CJ (2004) Expression of proinflammatory cytokines and growth factors at the injured growth plate cartilage in young rats. Bone 35(6):1307–1315PubMedCrossRefGoogle Scholar
  6. 6.
    Chung R, Cool JC, Scherer MA, Foster BK, Xian CJ (2006) Roles of neutrophil-mediated inflammatory response in the bony repair of injured growth plate cartilage in young rats. J Leukoc Biol 80(6):1272–1280PubMedCrossRefGoogle Scholar
  7. 7.
    Ueki M, Tanaka N, Tanimoto K, Nishio C, Honda K, Lin YY et al (2008) The effect of mechanical loading on the metabolism of growth plate chondrocytes. Ann Biomed Eng 36(5):793–800PubMedCrossRefGoogle Scholar
  8. 8.
    Winter DA (1983) Biomechanical motor patterns in normal walking. J Mot Behav 15(4):302–330PubMedGoogle Scholar
  9. 9.
    Kolf CM, Cho E, Tuan RS (2007) Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 9(1):204PubMedCrossRefGoogle Scholar
  10. 10.
    Ballock RT, O'Keefe RJ (2003) The biology of the growth plate. J Bone Joint Surg Am 85(4):715–726PubMedGoogle Scholar
  11. 11.
    MacRae VE, Farquharson C, Ahmed SF (2006) The pathophysiology of the growth plate in juvenile idiopathic arthritis. Rheumatology (Oxford) 45(1):11–19CrossRefGoogle Scholar
  12. 12.
    Simon S, Whiffen J, Shapiro F (1981) Leg-length discrepancies in monoarticular and pauciarticular juvenile rheumatoid arthritis. J Bone Joint Surg Am 63(2):209–215PubMedGoogle Scholar
  13. 13.
    Stokes IA, Aronsson DD, Dimock AN, Cortright V, Beck S (2006) Endochondral growth in growth plates of three species at two anatomical locations modulated by mechanical compression and tension. J Orthop Res 24(6):1327–1334PubMedCrossRefGoogle Scholar
  14. 14.
    Murakami S, Lefebvre V, de Crombrugghe B (2000) Potent inhibition of the master chondrogenic factor sox9 gene by interleukin-1 and tumor necrosis factor-alpha. J Biol Chem 275(5):3687–3692PubMedCrossRefGoogle Scholar
  15. 15.
    Gerstenfeld LC, Shapiro FD (1996) Expression of bone-specific genes by hypertrophic chondrocytes: Implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development. J Cell Biochem 62(1):1–9PubMedCrossRefGoogle Scholar
  16. 16.
    Pass C, MacRae VE, Ahmed SF, Farquharson C (2009) Inflammatory cytokines and the GH/IGF-I axis: novel actions on bone growth. Cell Biochem Funct 27(3):119–127PubMedCrossRefGoogle Scholar
  17. 17.
    Linsenmayer TF, Eavey RD, Schmid TM (1988) Type X collagen: a hypertrophic cartilage-specific molecule. Pathol Immunopathol Res 7(1–2):14–19PubMedCrossRefGoogle Scholar
  18. 18.
    Wilsman NJ, Farnum CE, Leiferman EM, Fry M, Barreto C (1996) Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. J Orthop Res 14(6):927–936PubMedCrossRefGoogle Scholar
  19. 19.
    Sandell LJ, Aigner T (2001) Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 3(2):107–113PubMedCrossRefGoogle Scholar
  20. 20.
    Long P, Gassner R, Agarwal S (2001) Tumor necrosis factor alpha-dependent proinflammatory gene induction is inhibited by cyclic tensile strain in articular chondrocytes in vitro. Arthritis Rheum 44(10):2311–2319PubMedCrossRefGoogle Scholar
  21. 21.
    Xu Z, Buckley MJ, Evans CH, Agarwal S (2000) Cyclic tensile strain acts as an antagonist of IL-1 beta actions in chondrocytes. J Immunol 165(1):453–460PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Karin Pichler
    • 1
  • Barbara Schmidt
    • 1
  • Eva E. Fischerauer
    • 1
  • Beate Rinner
    • 2
  • Gottfried Dohr
    • 3
  • Andreas Leithner
    • 4
  • Annelie M. Weinberg
    • 4
  1. 1.Department of Pediatric and Adolescent SurgeryMedical University GrazGrazAustria
  2. 2.Center for Medical Research – ZMFMedical University GrazGrazAustria
  3. 3.Institute of Cell Biology, Histology and Embryology, Center for Molecular MedicineMedical University of GrazGrazAustria
  4. 4.Department of Orthopaedic SurgeryMedical University of GrazGrazAustria

Personalised recommendations