Insulin-like growth factor (igf) binding protein-5201-218 region
regulates hydroxyapatite and igf-i binding.
Campbell, Phil G., and Dennis L. Andress.
Orthopaedic Research Laboratory, Allegheny University of the Health
Sciences, Pittsburgh, PA 15212, and the Departments of Medicine,
Veteran Affairs Medical Center and University of Washington, Seattle,
WA 98108.
APStracts 4:0167E, 1997.
Insulin-like growth factor binding protein-5 (IGFBP-5), the major bone
IGFBP, modifies the biological activity of IGFs within the
osteoblastic pericellular enviroment. Because glycosaminoglycans
modulate IGFBP-5 binding to osteoblast organic e_xtracellular matrix
(ECM), we assessed whether the heparin binding domain of IGFBP-5,
IGFBP-5201-218, modifies the interaction of IGFBP-5 with the
inorganic bone ECM, hydroxyapatite (HA). Synthetic IGFBP-5201-218
peptide increased the binding of IGFBP-5 to HA as well as the binding
of IGF-I to HA-bound IGFBP-5. This action was specific for the
heparin binding domain since IGFBP-5130-138, IGFBP-5138-152, and
IGFBP-51-169 were without effect. IGFBP-5201-218 was found to bind
directly to IGFBP-5 and cause a 3-fold enhancement of the IGF-I
binding affinity for IGFBP-5, whether IGFBP-5 was bound to HA or was
in a matrix-free fluid phase. Heparin inhibited the binding of IGFBP
-5 to HA and blocked the interaction of IGFBP-5 with IGFBP-5201-218 in
the fluid phase, suggesting that the primary heparin binding domain
of IGFBP-5 specifically enhances the binding of IGFBP-5 to HA and
increases IGF-I binding to IGFBP-5.
Received 26 March 1997; accepted in final form 23 July 1997.
APS Manuscript Number E139-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997