Carboxy-truncated insulin-like growth factor binding protein-5 stimulates mitogenesis in osteoblast-like cells

Biochem Biophys Res Commun. 1993 Aug 31;195(1):25-30. doi: 10.1006/bbrc.1993.2004.

Abstract

Recently we demonstrated that a 23 kDa form of IGFBP-5, derived from osteoblast-like cells, stimulates osteoblast mitogenesis and enhances IGF-I action. Because osteoblast-derived IGFBP-5 is smaller than recombinant intact IGFBP-5 (23 vs 30 kDa) and has decreased binding affinity for IGF-I, we proposed that the native 23 kDa form of IGFBP-5 was truncated at a carboxy-terminal position. We now show that a recombinant form of carboxy-truncated IGFBP-5 binds IGF-I with reduced affinity and stimulates mitogenesis in mouse osteoblasts. We also show that 125I-truncated IGFBP-5 specifically binds to osteoblast monolayers with low binding affinity, similar to that seen with native 23 kDa IGFBP-5. These data indicate that carboxy-truncated IGFBP-5 stimulates osteoblast mitogenesis and suggest that reduced IGF-binding and cell-surface attachment are local mediators of this response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Bone and Bones / cytology
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Humans
  • Insulin-Like Growth Factor Binding Protein 5
  • Insulin-Like Growth Factor I / metabolism*
  • Kinetics
  • Mice
  • Mitogens / pharmacology*
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteosarcoma
  • Polymerase Chain Reaction / methods
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Thymidine / metabolism
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Protein 5
  • Mitogens
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Insulin-Like Growth Factor I
  • Thymidine