Skip to main content
SpringerLink
Log in

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

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

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.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Fackler OT, Grosse R (2008) Cell motility through plasma membrane blebbing. J Cell Biol 181:879–884. doi:10.1083/jcb.200802081

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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/sj.gt.3301535

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka, 560-8531, Japan

    Masrina Mohd Nadzir & Masahito Taya

  2. Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Masahiro Kino-oka

  3. Japan Tissue Engineering Co., Ltd., 6-209-1 Miyakita-dori, Gamagori, Aichi, 443-0022, Japan

    Katsura Sugawara

Authors
  1. Masrina Mohd Nadzir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahiro Kino-oka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katsura Sugawara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masahito Taya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahito Taya.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 20 kb)

Supplementary material 2 (MPG 66 kb)

Supplementary material 3 (MPG 36 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nadzir, M.M., Kino-oka, M., Sugawara, K. et al. Modulation of chondrocyte migration and aggregation by insulin-like growth factor-1 in cultured cartilage. Biotechnol Lett 35, 295–300 (2013). https://doi.org/10.1007/s10529-012-1071-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-012-1071-8

Keywords

Search

Navigation