Cartilage is a primary target tissue for the IGFs. The mitogenic activity of these peptides is regulated by a family of high-affinity IGF-binding proteins (IGFBP-1 to -6). We characterized the IGFBPs produced by cultured chondrocytes derived from rib cartilage of prepubertal rabbits. Culture medium, which had been conditioned by these cells for 48 h showed bands of 22 kDa, 24 kDa and a 31/32 kDa doublet by Western ligand blotting with [(125)I]IGF-II. When the cells were grown in the presence of increasing amounts of IGF-I or IGF-II, the 31/32 kDa doublet increased in intensity (reaching a plateau of about 11-fold stimulation between 2 and 10 nM IGF-I). The 22 kDa and 24 kDa bands increased only slightly while a 26 kDa band became faintly visible. By Western immunoblotting the 31/32 kDa doublet was identified as IGFBP-5. An IGF-I analog with reduced affinity for IGFBPs, Long-R3 IGF-I, also induced IGFBP-5, while insulin was less effective (2.2-fold stimulation at 10 nM). IGF-I protected IGFBP-5 against proteolytic degradation by conditioned medium. IGF-I also enhanced the level of IGFBP-5 mRNA. LY294002, a specific inhibitor of the intracellular signaling molecule phosphatidylinositol 3-kinase, inhibited stimulation of IGFBP-5 by IGF-I. Dexamethasone suppressed IGFBP-5 (by 70% at 20 nM) but, at the same time, a 39/41 kDa doublet (presumably IGFBP-3) was induced. IGFBP-5 has been shown in several cell types to enhance the mitogenic activity of IGF-I. IGFBP-3 generally acts as a growth inhibitor. Therefore, the differential effects of dexamethasone on these regulatory proteins could account, at least in part, for the growth-arresting effect of this glucocorticoid.

This article has been cited by other articles:

				A I Martin, M Lopez-Menduina, E Castillero, M Granado, M A Villanua, and A Lopez-Calderon Ptgs2 activation by endotoxin mediates the decrease in Igf1, but not in Igfbp3, gene expression in the liver J. Endocrinol., August 1, 2008; 198(2): 385 - 394. [Abstract] [Full Text] [PDF]

				V E MacRae, C Farquharson, and S F Ahmed The restricted potential for recovery of growth plate chondrogenesis and longitudinal bone growth following exposure to pro-inflammatory cytokines. J. Endocrinol., May 1, 2006; 189(2): 319 - 328. [Abstract] [Full Text] [PDF]

				D. Kiepe, S. Ciarmatori, A. Hoeflich, E. Wolf, and B. Tonshoff Insulin-Like Growth Factor (IGF)-I Stimulates Cell Proliferation and Induces IGF Binding Protein (IGFBP)-3 and IGFBP-5 Gene Expression in Cultured Growth Plate Chondrocytes via Distinct Signaling Pathways Endocrinology, July 1, 2005; 146(7): 3096 - 3104. [Abstract] [Full Text] [PDF]

				T. Priego, M. Granado, A. I. Martin, A. Lopez-Calderon, and M. A. Villanua Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats J. Endocrinol., June 1, 2005; 185(3): 467 - 476. [Abstract] [Full Text] [PDF]

				B. C. J. van der Eerden, M. Karperien, and J. M. Wit Systemic and Local Regulation of the Growth Plate Endocr. Rev., December 1, 2003; 24(6): 782 - 801. [Abstract] [Full Text] [PDF]