Fibronectin fragments upregulate insulin-like growth factor binding proteins in chondrocytes.

Unlabelled: Addition of fibronectin fragments (Fn-fs) to cultured cartilage explants has been shown to mediate extensive cartilage matrix degradation followed by anabolic responses.

Objective: To determine whether specific Fn-fs regulate cartilage metabolism through a mechanism, in part, involving insulin-like growth factor (IGF) and insulin-like growth factor binding proteins (IGFBPs).

Methods: Primary bovine articular chondrocyte cultures were treated with Fn-fs.

Cell biology of osteoarthritis: the chondrocyte's response to injury.

Cartilage is comprised of a large amount of functional extracellular matrix that is made and maintained by a small number of chondrocytes, the sole resident cell type. Normal cartilage exists in a relatively steady state: that is, the anabolic processes (those that result in the synthesis of cartilage matrix components) are in equilibrium with the catabolic processes (those that result in the normal turnover of matrix molecules). If the functional extracellular matrix is disturbed by physical or molecular means, the cells respond in an attempt to repair the matrix.

Fibronectin-fragment-induced cartilage chondrolysis is associated with release of catabolic cytokines.

Fibronectin fragments have both catabolic and anabolic activities toward articular cartilage explants in vitro. Whereas a 1 nM concentration of an N-terminal 29 kDa fibronectin fragment (Fn-f) increases the proteoglycan (PG) content of cartilage without induction of matrix metalloproteinases (MMPs), 0.1-1 microM Fn-f temporarily suppresses PG synthesis and enhances MMP release.

Fibronectin fragments induce the expression of stromelysin-1 mRNA and protein in bovine chondrocytes in monolayer culture.

Addition of proteolytically generated fibronectin fragments (Fn-f) to cultured cartilage tissue causes greatly enhanced release of metalloproteinases (MMPs), such as pro-stromelysin-1 (proSln-1), and suppression of proteoglycan (PG) synthesis, through release of catabolic cytokines, while native fibronectin is ineffective. We have investigated whether enhanced release of proSln-1 was due to up-regulation of pro-Sln-1 mRNA. We report the addition of a 29-kDa (amino-terminal heparin-binding Fn-f) or a 140-kDa (central cell-binding Fn-f) to bovine chondrocytes in monolayer culture causes a dose dependent increase in the expression of pro-Sln-1 mRNA and the greatly enhanced release of pro-Sln-1 protein into the culture media.

Cloning of the rat insulin-like growth factor binding protein-1 gene and analysis of its 5' promoter region.

To understand specific mechanisms involved in the regulation of insulin-like growth factor binding protein-1 (IGFBP-1), an important modulator of IGF bioactivity, we cloned the rat IGFBP-1 gene and sequenced a 1.5 kb Sph1-Sph1 fragment containing 1110 bases upstream from the translation start site. Computer analysis reveals the presence of ATA, CACCC, and CCAAT elements, and putative homeodomain, AP-1, insulin and glucocorticoid response elements in the 5' promoter.