Antiproliferative effects of insulin-like growth factor-binding protein-3 in mesenchymal chondrogenic cell line RCJ3.1C5.18. Relationship to differentiation stage

Anna Spagnoli, Vivian Hwa, William A. Horton, Gregory P. Lunstrum, Charles T. Roberts, Francesco Chiarelli, Monica Torello, Ron G. Rosenfeld

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Abstract

Chondrogenesis results from a complex equilibrium between chondrocyte proliferation and differentiation. Insulin-like growth factors (IGFs) have a crucial role in chondrogenesis, but their mechanisms of action are not well defined. IGF-binding protein-3 (IGFBP-3) is the major carrier for circulating IGFs in postnatal life, and has been shown to have IGF-independent effects on proliferation of several cancer cell lines. In this study, we have evaluated the IGF-independent and -dependent effects of IGFBP-3 on chondrocyte proliferation and the relationship of these effects with chondrocyte differentiation stage. We used the RCJ3.1CS.18 nontransformed mesenchymal chondrogenic cell line, which, over 2 weeks of culture, progresses through the differentiation pathway exhibited by chondrocytes in the growth plate. We demonstrated that IGFBP-3 inhibited, in a dose-dependent manner (1-30 nM), the proliferation of chondroprogenitors and early differentiated chondrocytes, stimulated by des-(1-3)-IGF-I and longR3-IGF-I (IGF-I analogs with reduced affinity for IGFBP-3), and by insulin and IGF-I. In terminally differentiated chondrocytes, IGFBP-3 retained the ability to inhibit cell proliferation stimulated by IGF-I, but had no effect on cell growth stimulated by insulin, or des-(1-3)-IGF-I or longR3IGF-I. By monolayer affinity cross-linking, we demonstrated a specific IGFBP-3-associated cell-membrane protein of ∼20 kDa. We determined that IGFBP-3 has an antiproliferative effect on chondrocytes and, that this effect is related to the differentiation process. In chondroprogenitors and early differentiated chondrocytes, antiproliferative effect of IGFBP-3 is mainly IGF-independent, whereas, following terminal differentiation this effect is IGF-dependent.

Original languageEnglish (US)
Pages (from-to)5533-5540
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number8
DOIs
StatePublished - Feb 23 2001

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Insulin-Like Growth Factor Binding Protein 3
Chondrocytes
Somatomedins
Insulin-Like Growth Factor I
Cells
Cell Line
Chondrogenesis
Insulin
Growth Plate
Cell proliferation
Cell growth
Cell culture
Monolayers
Membrane Proteins
Cell Proliferation
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Antiproliferative effects of insulin-like growth factor-binding protein-3 in mesenchymal chondrogenic cell line RCJ3.1C5.18. Relationship to differentiation stage. / Spagnoli, Anna; Hwa, Vivian; Horton, William A.; Lunstrum, Gregory P.; Roberts, Charles T.; Chiarelli, Francesco; Torello, Monica; Rosenfeld, Ron G.

In: Journal of Biological Chemistry, Vol. 276, No. 8, 23.02.2001, p. 5533-5540.

Research output: Contribution to journalArticle

Spagnoli, Anna ; Hwa, Vivian ; Horton, William A. ; Lunstrum, Gregory P. ; Roberts, Charles T. ; Chiarelli, Francesco ; Torello, Monica ; Rosenfeld, Ron G. / Antiproliferative effects of insulin-like growth factor-binding protein-3 in mesenchymal chondrogenic cell line RCJ3.1C5.18. Relationship to differentiation stage. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 8. pp. 5533-5540.
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AU - Hwa, Vivian

AU - Horton, William A.

AU - Lunstrum, Gregory P.

AU - Roberts, Charles T.

AU - Chiarelli, Francesco

AU - Torello, Monica

AU - Rosenfeld, Ron G.

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