Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells

P. Grellier, D. Feliers, D. Yee, K. Woodruff, S. L. Abboud

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

IGF-I and -II play an important role in regulating bone formation. Bone marrow stromal cells, particularly those with osteoblast-like features, may act in concern with osteoblasts to increase IGF-I and -II levels in the bone microenvironment. Local bioavailability of IGFs, however, is modulated by IGF binding proteins (IGFBPs). We have previously demonstrated that murine TC-1 stromal cells constitutively secrete IGF-I and IGFBPs. In the present study, we determined the phenotype of these cells and used them as a model to explore the effect of IGFBPs on IGF-I-induced mitogenesis. The effect of IGF-I on IGFBPs expressed by TC-1 was also determined. When grown under conditions that promote osteogenic differentiation, TC-1 cells showed high alkaline phosphatase activity and mRNA levels, weakly expressed osteocalcin mRNA, and formed mineralized bone-like nodules. TC-1 cells expressed IGF-I and IGF-II mRNAs, while other stromal phenotypes preferentially expressed IGF-I. IGF-I stimulated TC-1 DNA synthesis in a dose-dependent manner and this effect was inhibited by recombinant IGFBP-1 and -4. Since IGF-I may regulate IGFBP production, the effect of IGF-I on IGFBPs expressed by TC-1 cells was determined. IGF-I increased the abundance of IGFBP-3, -4 and -5 in TC-1 conditioned medium, this correlated with induction of IGFBP-3 mRNA, but not with that of IGFBP-4 or -5 mRNAs. The findings demonstrate that most stromal cells express IGF-I which may act in an autocrine and/or paracrine fashion. The local effects of IGF-I, however, may be blocked by IGFBP-1 or -4. IGF-I regulates the relative abundance of IGFBPs in stromal cells which, in turn, may influence IGF-I-mediated effects on bone remodeling.

Original languageEnglish (US)
Pages (from-to)519-529
Number of pages11
JournalJournal of Endocrinology
Volume149
Issue number3
StatePublished - Jun 1996

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Insulin-Like Growth Factor Binding Proteins
Stromal Cells
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor II
Messenger RNA
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
Osteoblasts
Phenotype
Bone and Bones
Bone Remodeling
Osteocalcin
Conditioned Culture Medium
Mesenchymal Stromal Cells
Recombinant Proteins
Osteogenesis

ASJC Scopus subject areas

  • Endocrinology

Cite this

Grellier, P., Feliers, D., Yee, D., Woodruff, K., & Abboud, S. L. (1996). Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells. Journal of Endocrinology, 149(3), 519-529.

Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells. / Grellier, P.; Feliers, D.; Yee, D.; Woodruff, K.; Abboud, S. L.

In: Journal of Endocrinology, Vol. 149, No. 3, 06.1996, p. 519-529.

Research output: Contribution to journalArticle

Grellier, P, Feliers, D, Yee, D, Woodruff, K & Abboud, SL 1996, 'Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells', Journal of Endocrinology, vol. 149, no. 3, pp. 519-529.
Grellier, P. ; Feliers, D. ; Yee, D. ; Woodruff, K. ; Abboud, S. L. / Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells. In: Journal of Endocrinology. 1996 ; Vol. 149, No. 3. pp. 519-529.
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