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Functional role of endogenous latent TGF-beta activation in the intrinsic repair of mechanically loaded articular cartilage

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A novel approach for cartilage regeneration

Articular cartilage in synovial joints has a load- and friction-bearing function. Understanding how it maintains its activity for eight to nine decades is central to designing novel treatments for conditions such as osteoarthritis (OA).


Progressive degeneration of articular cartilage leads to the debilitating OA that is associated with pain and severe limitations in mobility. OA is highly prevalent amongst the EU population but the underlying mechanisms that defeat normal tissue maintenance and lead to joint degeneration are not fully elucidated. The key objective of the EU-funded CARTILAGE TGF-BETA (Functional role of endogenous latent TGF-beta activation in the intrinsic repair of mechanically loaded articular cartilage) project was to investigate the intrinsic repair mechanisms in articular cartilage. The consortium activities focused on the hypothesis that in response to physiologic mechanical loading, latent TGF-beta sequestered in the cartilage extracellular matrix becomes activated through the action of chondrocyte-secreted proteases. However, TGF-beta activation is unable to counterbalance degradation in cases of excessive loading and causes progressive degeneration of the tissue. The long-term goal was to assess if latent TGF-beta could serve as the basis for molecular inhibition and tissue engineering strategies to slow disease progression or replace defective articular cartilage. Towards this goal, researchers developed an experimental in vitro system and demonstrated for the first time that endogenous TGF-beta played an important functional role in protecting articular cartilage subjected to mechanical loading. Activation of endogenous TGF-beta maintained tensile integrity of the collagen matrix and chondrocyte viability when the tissue was mechanically loaded. As a regenerative approach, scientists adopted a novel biomimetic cartilage tissue strategy, where latent TGF-beta was conjugated to a cell encapsulated hydrogel scaffold. This approach mimicked the native environment of articular cartilage and offered uniform growth factor activity for tissue engineering purposes. In another part of the project, the consortium characterised the make-up and distribution of the cartilage extracellular matrix components. The hyperspectral Raman imaging technique was used as it offered the capacity to characterise the quality and integrity of engineered cartilage. Considering the socioeconomic burden of OA in Europe, the mechanistic insight generated during the CARTILAGE TGF-BETA study provides a novel regenerative approach based on cartilage biosynthesis.


Articular cartilage, osteoarthritis, CARTILAGE TGF-BETA, TGB-beta, tissue engineering

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