Accumulation of Exogenous Activated TGF-¦Â in the Superficial Zone of?Articular Cartilage

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• 作者：Michael B. Albro^&dagger ; ; ^{mba2103@columbia.edu} ; Robert J. Nims^&Dagger ; ; Alexander D. Cigan^&Dagger ; ; Kevin J. Yeroushalmi^&Dagger ; ; Tamara Alliston^§ ; ; Clark T. Hung^&Dagger ; ; Gerard A. Ateshian^&dagger ; ; ^&Dagger ;
• 刊名：Biophysical Journal
• 出版年：2013
• 出版时间：16 April, 2013
• 年：2013
• 卷：104
• 期：8
• 页码：1794-1804
• 全文大小：341 K

文摘

It was recently demonstrated that mechanical shearing of synovial fluid (SF), induced during joint motion, rapidly activates latent transforming growth factor ¦Â (TGF-¦Â). This discovery raised the possibility of a physiological process consisting of latent TGF-¦Â supply to SF, activation via shearing, and transport of TGF-¦Â into the cartilage matrix. Therefore, the two primary objectives of this investigation were to characterize the secretion rate of latent TGF-¦Â into SF, and the transport of active TGF-¦Â across the articular surface and into the cartilage layer. Experiments on tissue explants demonstrate that high levels of latent TGF-¦Â1 are secreted from both the synovium and all three articular cartilage zones (superficial, middle, and deep), suggesting that these tissues are capable of continuously replenishing latent TGF-¦Â to SF. Furthermore, upon exposure of cartilage to active TGF-¦Â1, the peptide accumulates in the superficial zone (SZ) due to the presence of an overwhelming concentration of nonspecific TGF-¦Â binding sites in the extracellular matrix. Although this response leads to high levels of active TGF-¦Â in the SZ, the active peptide is unable to penetrate deeper into the middle and deep zones of cartilage. These results provide strong evidence for a sequential physiologic mechanism through which SZ chondrocytes gain access to active TGF-¦Â: the synovium and articular cartilage secrete latent TGF-¦Â into the SF and, upon activation, TGF-¦Â transports back into the cartilage layer, binding exclusively to the SZ.