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• W2007449623 startingPage "1765" @default.
• W2007449623 abstract "Abstract During aging, chondrocytes become unresponsive to insulin‐like growth factor‐I (IGF‐I). This study examined the role of Cdc42 ( c ell‐ d ivision‐ c ycle 42) in IGF‐I signaling during aging. Experiments were performed using cartilage and chondrocytes isolated from horses ages 1 day–25 years. Northern analysis was used to examine expression of the small GTPases Cdc42, Rac, and RhoA. Western analysis was utilized to assess total Cdc42 (GTP + GDP‐bound); active, GTP‐Cdc42 was assessed using a pulldown assay with Western analysis. GTP‐Cdc42 was also measured following IGF‐I treatment. Gene expression for Cdc42 and Rac were decreased in mature samples, but there was no difference in total Cdc42 (GTP + GDP‐bound) protein expression due to age. GTP‐Cdc42 was significantly greater in prepubescent samples compared to other age groups. IGF‐I diminished the GTP‐bound state of Cdc42 in prepubescent chondrocytes; however, this effect was lost during aging. No differences in results were observed due to sample type; that is, cartilage tissues versus isolated chondrocytes. These studies suggest that loss of IGF‐I‐mediated regulation of Cdc42 activation may be a mechanism for the chondrocyte unresponsive state during aging. Further, the activation state of Cdc42, measured in native and IGF‐I‐treated cartilage tissue for the first time, is similar to that of isolated chondrocytes, indicating that the activation state of small G‐proteins is not affected by isolation of chondrocytes from the extracellular matrix. Continued studies will identify the upstream regulators of Cdc42, which will further elucidate the molecular mechanism of IGF‐I resistance during aging thereby providing insight into targeted strategies for age‐related osteoarthritis. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1765–1772, 2006" @default.
• W2007449623 created "2016-06-24" @default.
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• W2007449623 date "2006-07-10" @default.
• W2007449623 modified "2023-10-13" @default.
• W2007449623 title "Signaling through the small G-protein Cdc42 is involved in insulin-like growth factor-I resistance in aging articular chondrocytes" @default.
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• W2007449623 doi "https://doi.org/10.1002/jor.20185" @default.
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