Dynamic mechanical compression of devitalized articular cartilage does not activate latent TGF-β

A growing body of research has highlighted the role that mechanical forces play in the activation of latent TGF-beta in biological tissues. In synovial joints, it has recently been demonstrated that the mechanical shearing of synovial fluid, induced during joint motion, rapidly activates a large fraction of its soluble latent TGF-beta content. Based on this observation, the primary hypothesis of the current study is that the mechanical deformation of articular cartilage, induced by dynamic joint motion, can similarly activate the large stores of latent TGF-beta bound to the tissue extracellular matrix (ECM). Here, devitalized deep zone articular cartilage cylindrical explants (n=84) were subjected to continuous dynamic mechanical loading (low strain: +/- 2% or high strain: +/- 7.5% at 0.5 Hz) for up to 15 h or maintained unloaded. TGF-beta activation was measured in these samples over time while accounting for the active TGF-beta that remains bound to the cartilage ECM. Results indicate that TGF-beta 1 is present in cartilage at high levels (68.5 +/- 20.6 ng/mL) and resides predominantly in the latent form (>98% of total). Under dynamic loading, active TGF-beta 1 levels did not statistically increase from the initial value nor the corresponding unloaded control values for any test, indicating that physiologic dynamic compression of cartilage is unable to directly activate ECM-bound latent TGF-beta via purely mechanical pathways and leading us to reject the hypothesis of this study. These results suggest that deep zone articular chondrocytes must alternatively obtain access to active TGF-beta through chemical-mediated activation and further suggest that mechanical deformation is unlikely to directly activate the ECM-bound latent TGF-beta of various other tissues, such as muscle, ligament, and tendon. (C) 2013 Elsevier Ltd. All rights reserved.