title: Accumulation of exogenous activated TGF-β in the superficial zone of articular cartilage.
abstract: It was recently demonstrated that mechanical shearing of synovial fluid (SF), induced during joint motion, rapidly activates latent transforming growth factor β (TGF-β). This discovery raised the possibility of a physiological process consisting of latent TGF-β supply to SF, activation via shearing, and transport of TGF-β into the cartilage matrix. Therefore, the two primary objectives of this investigation were to characterize the secretion rate of latent TGF-β into SF, and the transport of active TGF-β across the articular surface and into the cartilage layer. Experiments on tissue explants demonstrate that high levels of latent TGF-β1 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-β to SF. Furthermore, upon exposure of cartilage to active TGF-β1, the peptide accumulates in the superficial zone (SZ) due to the presence of an overwhelming concentration of nonspecific TGF-β binding sites in the extracellular matrix. Although this response leads to high levels of active TGF-β 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-β: the synovium and articular cartilage secrete latent TGF-β into the SF and, upon activation, TGF-β transports back into the cartilage layer, binding exclusively to the SZ.
authors.affiliation: Department of Mechanical Engineering, Columbia University, New York, New York, USA. mba2103@columbia.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Albro
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nims
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cigan
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Yeroushalmi
authors.forename: Tamara
authors.initials: T
authors.lastname: Alliston
authors.forename: Clark T
authors.initials: CT
authors.lastname: Hung
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Ateshian
mesh_terms: D000818:Animals; D001665:Binding Sites; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D019902:Chondrocytes / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D013582:Synovial Fluid / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta