Endocrinology, Vol 137, 4665-4670, Copyright © 1996 by Endocrine Society

ARTICLES

Autocrine down-regulation of collagenase-3 in rat bone cell cultures by insulin-like growth factors

AM Delany, S Rydziel and E Canalis
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.

Insulin-like growth factors (IGF)-I and -II are presumed to act as autocrine regulators of bone formation. Recently, we demonstrated that IGF-I and -II inhibit bone collagen degradation and collagenase-3 synthesis in osteoblast cultures. Therefore, we tested the autocrine role of IGFs in the endogenous expression of collagenase-3 in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). Steady-state messenger RNA (mRNA) levels were determined by Northern blot analysis and collagenase concentrations in the culture medium were determined by Western immunoblot. Basal level collagenase-3 transcripts decreased in Ob cell cultures, coinciding with an increase in IGF-I and -II protein levels. Removal of the conditioned medium modestly increased collagenase-3 mRNA levels and restored the ability of exogenously added IGF-I to repress collagenase-3 transcripts. IGF neutralizing antibodies and IGF binding proteins-2 and -3 in excess increased and sustained collagenase mRNA, heterogeneous nuclear RNA, and protease levels in Ob cell cultures. In conclusion, IGF-I and -II are autocrine repressors of collagenase-3 synthesis, and this effect may contribute to their actions on the maintenance of a normal bone collagen matrix.

This article has been cited by other articles:

				C. A. Conover Insulin-like growth factor-binding proteins and bone metabolism Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E10 - E14. [Abstract] [Full Text] [PDF]

				H.-J. Im, C. Pacione, S. Chubinskaya, A. J. van Wijnen, Y. Sun, and R. F. Loeser Inhibitory Effects of Insulin-like Growth Factor-1 and Osteogenic Protein-1 on Fibronectin Fragment- and Interleukin-1{beta}-stimulated Matrix Metalloproteinase-13 Expression in Human Chondrocytes J. Biol. Chem., July 3, 2003; 278(28): 25386 - 25394. [Abstract] [Full Text] [PDF]

				S. Onodera, J. Nishihira, K. Iwabuchi, Y. Koyama, K. Yoshida, S. Tanaka, and A. Minami Macrophage Migration Inhibitory Factor Up-regulates Matrix Metalloproteinase-9 and -13 in Rat Osteoblasts. RELEVANCE TO INTRACELLULAR SIGNALING PATHWAYS J. Biol. Chem., March 1, 2002; 277(10): 7865 - 7874. [Abstract] [Full Text] [PDF]

				R. C. Pereira, V. Jorgetti, and E. Canalis Triiodothyronine induces collagenase-3 and gelatinase B expression in murine osteoblasts Am J Physiol Endocrinol Metab, September 1, 1999; 277(3): E496 - E504. [Abstract] [Full Text] [PDF]

				E. Gazzerro, S. Rydziel, and E. Canalis Skeletal Bone Morphogenetic Proteins Suppress the Expression of Collagenase-3 by Rat Osteoblasts Endocrinology, February 1, 1999; 140(2): 562 - 567. [Abstract] [Full Text]

				T. Kawane and N. Horiuchi Insulin-Like Growth Factor I Suppresses Parathyroid Hormone (PTH)/PTH-Related Protein Receptor Expression via a Mitogen-Activated Protein Kinase Pathway in UMR-106 Osteoblast-Like Cells Endocrinology, February 1, 1999; 140(2): 871 - 879. [Abstract] [Full Text]

				B. Gabbitas and E. Canalis Insulin-like growth factors sustain insulin-like growth factor-binding protein-5 expression in osteoblasts Am J Physiol Endocrinol Metab, August 1, 1998; 275(2): E222 - E228. [Abstract] [Full Text] [PDF]

				N. Franchimont, S. Rydziel, A. M. Delany, and E. Canalis Interleukin-6 and Its Soluble Receptor Cause a Marked Induction of Collagenase 3 Expression in Rat Osteoblast Cultures J. Biol. Chem., May 2, 1997; 272(18): 12144 - 12150. [Abstract] [Full Text] [PDF]

				S. K. Winchester, N. Selvamurugan, R. C. D'Alonzo, and N. C. Partridge Developmental Regulation of Collagenase-3 mRNA in Normal, Differentiating Osteoblasts through the Activator Protein-1 and the runt Domain Binding Sites J. Biol. Chem., July 21, 2000; 275(30): 23310 - 23318. [Abstract] [Full Text] [PDF]