Journal of Clinical Endocrinology & Metabolism, Vol 81, 1096-1103, Copyright © 1996 by Endocrine Society

ARTICLES

Chondrocytes from osteoarthritic cartilage have increased expression of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP- 3) and -5, but not IGF-II or IGFBP-4

RC Olney, K Tsuchiya, DM Wilson, M Mohtai, WJ Maloney, DJ Schurman and RL Smith
Department of Pediatrics, Stanford University Medical Center, California 94305, USA.

Osteoarthritis is a disease in which articular cartilage metabolism is altered, leading to cartilage destruction. As insulin-like growth factor-I (IGF-I) is the major anabolic mediator for articular cartilage, and the IGF-binding proteins (IGFBPs) are an integral part of the IGF axis, they may play a role in the pathophysiology of osteoarthritis. Chondrocytes isolated from fibrillated and normal appearing areas of osteoarthritic human cartilage and from normal cartilage were studied for IGF and IGFBP expression. IGF and IGFBP messenger ribonucleic acids were analyzed by a RT-quantitative PCR technique and Northern blotting. In osteoarthritic chondrocytes, IGF-I message was increased 3.5-fold, IGFBP-3 was increased 24-fold, and IGFBP-5 was increased 16-fold over normal chondrocytes. Chondrocytes from normal appearing areas of cartilage from osteoarthritic joints had intermediate levels. Message levels for beta-actin, IGF-II, and IGFBP-4 were unchanged between the cartilage types. IGF and IGFBP production were analyzed by Western ligand blots and RIAs of conditioned medium from cartilage cultured in serum-free conditions. IGF-I was undetectable in conditioned medium from normal cartilage and increased in that from osteoarthritic cartilage. Osteoarthritic cartilage samples produced IGFBP-2, -3, and -4; glycosylated IGFBP-4; and IGFBP-5. IGFBP- 2, -3, and -5 production was increased in osteoarthritic cartilage. Proteases with activity against IGFBP-3 and -5 were also produced by osteoarthritic cartilage. The observation that IGFBP-3 and -5 expression and production are elevated in osteoarthritic cartilage suggests that they may be acting as a competitor for IGF-I in osteoarthritic cartilage, thus reducing the anabolic stimulation of this tissue and contributing to the net loss of cartilage in this disease.

This article has been cited by other articles:

				C. Merrihew, S. Soeder, D. C. Rueger, K. E. Kuettner, and S. Chubinskaya Modulation of Endogenous Osteogenic Protein-1 (OP-1) by Interleukin-1 in Adult Human Articular Cartilage J. Bone Joint Surg. Am., August 1, 2003; 85(90003): 67 - 74. [Abstract] [Full Text] [PDF]

				N. R. Bhakta, A. M. Garcia, E. H. Frank, A. J. Grodzinsky, and T. I. Morales The Insulin-like Growth Factors (IGFs) I and II Bind to Articular Cartilage via the IGF-binding Proteins J. Biol. Chem., February 25, 2000; 275(8): 5860 - 5866. [Abstract] [Full Text] [PDF]

				T. L. Bushman and J. F. Kuemmerle IGFBP-3 and IGFBP-5 production by human intestinal muscle: reciprocal regulation by endogenous TGF-beta 1 Am J Physiol Gastrointest Liver Physiol, December 1, 1998; 275(6): G1282 - G1290. [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]