Endocrinology, Vol 124, 2365-2372, Copyright © 1989 by Endocrine Society

ARTICLES

Production of insulin-like growth factors and their binding proteins by rabbit articular chondrocytes: relationships with cell multiplication

B Froger-Gaillard, P Hossenlopp, M Adolphe and M Binoux
Laboratoire de Pharmacologie Cellulaire de l'Ecole Pratique des Hautes Etudes, Universite Paris VI, France.

Articular chondrocytes from 2- to 3-month-old rabbits were cultured in serum-free medium supplemented with fibroblast growth factor. The effects were studied of GH, insulin-like growth factors (IGFs), and insulin on the production of IGF-I, IGF-II, and their binding proteins (BPs) and on cell multiplication. In the control culture medium, IGF-I levels were about one fifth those of IGF-II. Western blot analysis of the BPs revealed a predominant 30K form and 24K and 20K forms which appeared inconsistently and in small quantities. Ten to 100 ng/ml human GH had no mitogenic effect, and even had a slightly inhibitory effect. IGF-I at 10 ng/ml stimulated cell multiplication above the control level by 41% and at 50 ng/ml by 74%, whereas the mean increase obtained with IGF-II (10 and 50 ng/ml) was only 19%. At the same doses, insulin had no effect, but at 5 micrograms/ml it stimulated cell multiplication by a mean of 67%. There was a positive correlation between cell number and release into the medium of both IGF-I (r = 0.86) and IGF-II (r = 0.77). Neither IGF-I nor IGF-II production was affected by GH. Insulin (5 micrograms/ml) increased IGF-I production by a factor of 2.6, but increased IGF-II production by a factor of only 1.4. Under the various conditions of culture with different doses of GH and insulin, cell multiplication, relative to the control value was positively correlated to the IGF-I/IGF-II production ratio (r = 0.77). It would, therefore, seem that IGF-I secreted by the chondrocytes may stimulate their own proliferation. When IGFs or insulin were added to the culture medium, changes in the electrophoretic profiles of the BPs included an increase in the 30K form and an increase in or the appearance of the 24K and 20K forms. Ten and 50 ng/ml IGF-I or IGF-II had effects equal to or greater than those induced by 5 micrograms/ml insulin. These results indicate that the syntheses of BPs and IGFs are coordinated and that IGFs may be implicated in the control of the synthesis of their BPs.

This article has been cited by other articles:

				M. Reinecke, A. C. Schmid, B. Heyberger-Meyer, E. B. Hunziker, and J. Zapf Effect of Growth Hormone and Insulin-Like Growth Factor I (IGF-I) on the Expression of IGF-I Messenger Ribonucleic Acid and Peptide in Rat Tibial Growth Plate and Articular Chondrocytes in Vivo Endocrinology, August 1, 2000; 141(8): 2847 - 2853. [Abstract] [Full Text] [PDF]

				K. Sagawa, B. Han, D. C. DuBois, H. Murer, R. R. Almon, and M. E. Morris Age- and Growth Hormone-Induced Alterations in Renal Sulfate Transport J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1182 - 1187. [Abstract] [Full Text]

				K. M. Kelley, T. R. Johnson, J. Ilan, and R. W. Moskowitz Glucose regulation of the IGF response system in chondrocytes: induction of an IGF-I-resistant state Am J Physiol Regulatory Integrative Comp Physiol, April 1, 1999; 276(4): R1164 - R1171. [Abstract] [Full Text] [PDF]

				D. Sunic, J. D. McNeil, T. E. Rayner, D. L. Andress, and D. A. Belford Regulation of Insulin-Like Growth Factor-Binding Protein-5 by Insulin-Like Growth Factor I and Interleukin-1{alpha} in Ovine Articular Chondrocytes Endocrinology, May 1, 1998; 139(5): 2356 - 2362. [Abstract] [Full Text] [PDF]

				M. Takigawa, T. Okawa, H.-O. Pan, C. Aoki, K. Takahashi, J.-D. Zue, F. Suzuki, and A. Kinoshita Insulin-Like Growth Factors I and II Are Autocrine Factors in Stimulating Proteoglycan Synthesis, a Marker of Differentiated Chondrocytes, Acting through Their Respective Receptors on a Clonal Human Chondrosarcoma-Derived Chondrocyte Cell Line, HCS-2/8 Endocrinology, October 1, 1997; 138(10): 4390 - 4400. [Abstract] [Full Text] [PDF]

				D. R. Powell, F. Liu, B. K. Baker, R. L. Hintz, S. K. Durham, E. D. Brewer, J. W. Frane, B. Tonshoff, O. Mehls, A.-M. Wingen, et al. Insulin-Like Growth Factor-Binding Protein-6 Levels Are Elevated in Serum of Children with Chronic Renal Failure: A Report of the Southwest Pediatric Nephrology Study Group J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2978 - 2984. [Abstract] [Full Text] [PDF]