Does mechanical loading activate articular cartilage TGF-Beta?

Since LSJL loads the articular cartilage which is part of the synovial joint this study may have implications on LSJL.

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

mechanical shearing of synovial fluid, induced during joint motion, rapidly activates a large fraction of its soluble latent TGF-β 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-β 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 0.5Hz) for up to 15h or maintained unloaded. TGF-β activation was measured in these samples over time while accounting for the active TGF-β that remains bound to the cartilage ECM. Results indicate that TGF-β1 is present in cartilage at high levels (68.5±20.6ng/mL) and resides predominantly in the latent form (>98% of total). Under dynamic loading, active TGF-β1 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-β 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-β through chemical-mediated activation and further suggest that mechanical deformation is unlikely to directly activate the ECM-bound latent TGF-β of various other tissues, such as muscle, ligament, and tendon{or bones?}.”

If the TGF-Beta of the synovial joint is the only location can be activated it could explain why it is important to load there.

” During joint motion, opposing articular surfaces slide relative to one another, producing high levels of mechanical fluid shear (~ 104 s−1) in the synovial fluid”

” due to the presence of an overwhelming supply of non-specific binding sites in the cartilage ECM, active TGF-β from an external bathing solution predominantly binds to, and accumulates in the superficial zone (0–250 µm deep) and is unable to penetrate deeper into articular cartilage”

“TGF-β activated in synovial fluid can reach high concentrations in superficial articular cartilage, but it is unable to transport into the middle and deep zones of the tissue.”

” the shear rates of pressure-driven fluid flow through the interstitium of the tissue are far lower than those experienced in synovial fluid”

“mechanical loading in live tissue may alternatively modulate the secretion of various chemical activation mediators, such as MMPs and other proteases, and thus indirectly induce TGF-β activation.”

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