Biotechnology Letters

, Volume 35, Issue 2, pp 295–300 | Cite as

Modulation of chondrocyte migration and aggregation by insulin-like growth factor-1 in cultured cartilage

  • Masrina Mohd Nadzir
  • Masahiro Kino-oka
  • Katsura Sugawara
  • Masahito TayaEmail author
Original Research Paper


The effect of insulin-like growth factor-1 (IGF-1) on the behavior of rabbit chondrocytes in cultured collagen (CL) gels initially seeded with 2 × 105 cells/ml was examined. On day 5, the frequency of migrating cells cultured in presence of 100 ng IGF-1/ml was 0.04, which was 54 % of the frequency in IGF-1-free culture. The presence of IGF-1 caused an increase in the frequency of dividing cells from 0.09 to 0.13. These results suggest that IGF-1 suppressed the migration of chondrocytes in the CL gels while stimulating cell division in the initial culture phase. The proteolytic migration of cells was thought to be suppressed by the down-regulation of membrane type 1 matrix metalloproteinase by IGF-1. This contributed to the formation of aggregates with spherical-shaped cells that produced collagen type II.


Aggregate formation Cell migration Chondrocyte cells Cultured cartilage Insulin-like growth factor-1 Tissue engineering 

Supplementary material

10529_2012_1071_MOESM1_ESM.doc (20 kb)
Supplementary material 1 (DOC 20 kb)

Supplementary material 2 (MPG 66 kb)

Supplementary material 3 (MPG 36 kb)


  1. Bhardwaj N, Nguyen QT, Chen AC, Kaplan DL, Sah RL, Kundu SC (2011) Potential of 3-D tissue constructs engineered from bovine chondrocytes/silk fibroin-chitosan for in vitro cartilage tissue engineering. Biomaterials 32:5773–5781. doi: 10.1016/j.biomaterials.2011.04.061 PubMedCrossRefGoogle Scholar
  2. Devreotes PN, Zigmond SH (1988) Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. Annu Rev Cell Biol 4:649–686. doi: 10.1146/annurev.cb.04.110188.003245 PubMedCrossRefGoogle Scholar
  3. Fackler OT, Grosse R (2008) Cell motility through plasma membrane blebbing. J Cell Biol 181:879–884. doi: 10.1083/jcb.200802081 PubMedCrossRefGoogle Scholar
  4. Fortier LA, Lust G, Mohammed HO, Nixon AJ (1999) Coordinate upregulation of cartilage matrix synthesis in fibrin cultures supplemented with exogenous insulin-like growth factor-I. J Orthop Res 17:467–474. doi: 10.1002/jor.1100170403 PubMedCrossRefGoogle Scholar
  5. Khoshfetrat AB, Kino-oka M, Takezawa Y, Yamamoto T, Sugawara K, Taya M (2009) Seeding density modulates migration and morphology of rabbit chondrocytes cultured in collagen gels. Biotechnol Bioeng 102:294–302. doi: 10.1002/bit.22029 PubMedCrossRefGoogle Scholar
  6. Kim K-W, Ha K-Y, Park J-B, Woo Y-K, Chung H-N, An HS (2005) Expression of membrane-type I matrix metalloproteinase, Ki-67 protein, and type II collagen by chondrocytes migrating from cartilage endplate into nucleus pulposus in rat intervertebral discs: a cartilage endplate-fracture model using an intervertebral disc organ culture. Spine 30:1373–1378. doi: 10.1097/01.brs.0000166155.48168.0e PubMedCrossRefGoogle Scholar
  7. Kino-oka M, Yashiki S, Ota Y, Mushiaki Y, Sugawara K, Yamamoto T, Takezawa T, Taya M (2005) Subculture of chondrocytes on a collagen type I-coated substrate with suppressed cellular dedifferentiation. Tissue Eng 11:597–608. doi: 10.1089/ten.2005.11.597 PubMedCrossRefGoogle Scholar
  8. Kino-oka M, Maeda Y, Sato Y, Khoshfetrat AB, Yamamoto T, Sugawara K, Taya M (2008) Characterization of spatial growth and distribution of chondrocyte cells embedded in collagen gels through a stereoscopic cell imaging system. Biotechnol Bioeng 99:1230–1240. doi: 10.1002/bit.21667 PubMedCrossRefGoogle Scholar
  9. Kino-oka M, Kagita S, Nadzir MM, Inoue H, Sugawara K, Taya M (2010) Direct measurement of oxygen concentration inside cultured cartilage for relating to spatial growth of rabbit chondrocytes. J Biosci Bioeng 110:363–366. doi: 10.1016/j.jbiosc.2010.03.009 PubMedCrossRefGoogle Scholar
  10. Loeser RF, Pacione CA, Chubinskaya S (2003) The combination of insulin-like growth factor-1 and osteogenic protein-1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis Rheum 48:2188–2196. doi: 10.1002/art.11209 PubMedCrossRefGoogle Scholar
  11. Luyten FP, Hascall VC, Nissley SP, Morales TI, Reddi AH (1988) Insulin-like growth factors maintain steady-state metabolism of proteoglycans in bovine articular cartilage explants. Arch Biochem Biophys 267:416–425. doi: 10.1016/0003-9861(88)90047-1 PubMedCrossRefGoogle Scholar
  12. Madry H, Zurakowski D, Trippel SB (2001) Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation. Gene Ther 8:1443–1449. doi: 10.1038/ PubMedCrossRefGoogle Scholar
  13. Mira E, Mañes S, Lacalle RA, Márquez G, Martínez AC (1999) Insulin-like growth factor I-triggered cell migration and invasion are mediated by matrix metalloproteinase-9. Endocrinology 140:1657–1664. doi: 10.1210/en.140.4.1657 PubMedCrossRefGoogle Scholar
  14. 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 17:475–487. doi: 10.1002/jor.1100170404 PubMedCrossRefGoogle Scholar
  15. Ochi M, Uchio Y, Kawasaki K, Wakitani S, Iwasa J (2002) Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. J Bone Joint Surg Br 84-B:571–578. doi: 10.1302/0301-620X.84B4.11947 CrossRefGoogle Scholar
  16. Rogachefsky RA, Dean DD, Howell DS, Altman RD (1993) Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate. Osteoarthritis Cartilage 1:105–114. doi: 10.1016/S1063-4584(05)80025-1 PubMedCrossRefGoogle Scholar
  17. Wolf K, Mazo I, Leung H, Engelke K, von Adrian UH, Deryugina EI, Strongin AY, Bröcker E-B, Friedl P (2003) Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160:267–277. doi: 10.1083/jcb.200209006 PubMedCrossRefGoogle Scholar
  18. Zhang D, Brodt P (2003) Type 1 insulin-like growth factor regulates MT1-MMP synthesis and tumor invasion via PI 3-kinase/Akt signaling. Oncogene 22:974–982. doi: 10.1038/sj.onc.1206197 PubMedCrossRefGoogle Scholar
  19. Zhang D, Bar-Eli M, Meloche S, Brodt P (2004) Dual regulation of MMP-2 expression by the type 1 insulin-like growth factor receptor: the phosphatidylinositol 3-kinase/Akt and Raf/ERK pathways transmit opposing signals. J Biol Chem 279:19683–19690. doi: 10.1074/jbc.M313145200 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Masrina Mohd Nadzir
    • 1
  • Masahiro Kino-oka
    • 2
  • Katsura Sugawara
    • 3
  • Masahito Taya
    • 1
    Email author
  1. 1.Division of Chemical EngineeringGraduate School of Engineering Science, Osaka UniversityToyonakaJapan
  2. 2.Department of BiotechnologyGraduate School of Engineering, Osaka UniversitySuitaJapan
  3. 3.Japan Tissue Engineering Co., Ltd.GamagoriJapan

Personalised recommendations