Age‐related decline in chondrocyte response to insulin‐like growth factor‐I: The role of growth factor binding proteins

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Abstract

<jats:title>Abstract</jats:title><jats:p>The synthetic activity of chondrocytes in articular cartilage declines with age, possibly as a result of decreased sensitivity to anabolic growth factors such as insulin‐like growth factor‐I. The sensitivity of these cells to insulin‐like growth factor‐I is regulated, in pan, by the synthesis of insulin‐like growth factor‐I binding proteins. We hypothesized that, as cartilage ages, an increase in the expression of these binding proteins suppresses the synthetic response of chondrocytes to insulin‐like growth factor‐I, To test this hypothesis, we measured proteoglycan synthesis (incorporation of [<jats:sup>35</jats:sup>S]sulfate per cell) in alginate cultures of chondrocytes from the articular cartilage of 1,3, 12, and 24‐month‐old rats. A dose‐response to insulin‐like growth factor‐I was determined for cells from each age group; incorporation of [<jats:sup>35</jats:sup>S]sulfate per cell declined with age, regardless of the dose. The sharpest decline was found between cells from the 1 and 3‐month‐old groups. Using the Western ligand b ot technique, we then compared the expression of insulin‐like growth factor‐1 binding protein in chondrocytes from the 1 and 3‐month‐old rats and found that it was increased in the cells from the older animals. Recombinant insulin‐like growth factor‐3, when added to the cell cultures of the 1‐month‐old rats, inhibited incorporation of [<jats:sup>35</jats:sup>S]sulfate and blocked responses to insulin‐like growth factor‐I. These findings suggest that the age‐related decline in the synthetic response of chondrocytes to insulin‐like growth factor‐I results, at least in part, from increased expression of insulin‐like growth factor binding protein.</jats:p>

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