Role of extracellular matrix in insulin-like growth factor (IGF) binding protein-2 regulation of IGF-II action in normal human osteoblasts

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41 Scopus citations

Abstract

Insulin-like growth factor binding protein-2 (IGFBP-2) in its native form had little affinity for extracellular matrix (ECM) derived from human or rat osteoblastic cells. However, in the presence of IGFs, IGFBP-2 binding to ECM was markedly enhanced, with IGF-II being more effective than IGF-I. IGF-II-enhanced binding of IGFBP-2 to ECM was specific for IGFBP-2 of the six known IGFBPs. In the presence of IGF-II, IGFBP-2 bound with high affinity to heparin-Sepharose, but not to type I collagen, fibronectin, or laminin. Furthermore, heparin and heparan sulfate, but not chondroitin sulfate, inhibited IGFBP-2/IGF-II binding to ECM. High salt (100 mM NaCl) inhibited, while CaCl2 enhanced binding of IGFBP-2/IGF-II to ECM. In the presence of ECM, IGFBP-2/IGF-II was as effective as IGF-II alone in stimulating [3H]thymidine and [3H]proline incorporation and in inhibiting apoptosis in cultured human osteoblasts. On the other hand, IGFBP-2 was a potent inhibitor of IGF-II action in human breast and ovarian carcinoma cells. There was no difference between soluble and ECM-associated IGFBP-2 in affinity for IGF-I and IGF-II. These data suggest a unique mechanism for targeting an anabolic IGFBP-2/IGF-II complex in bone.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalGrowth Hormone and IGF Research
Volume13
Issue number6
DOIs
StatePublished - Dec 2003

Keywords

  • Extracellular matrix
  • Insulin-like growth factor binding protein-2
  • Insulin-like growth factor-II
  • Osteoblasts

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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