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

ABSTRACT: A growing body of research has highlighted the role that mechanical forces play in the activation of latent TGF-? 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-? 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-? 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-? activation was measured in these samples over time while accounting for the active TGF-? that remains bound to the cartilage ECM. Results indicate that TGF-?1 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-?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-? 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-? through chemical-mediated activation and further suggest that mechanical deformation is unlikely to directly activate the ECM-bound latent TGF-? of various other tissues, such as muscle, ligament, and tendon.

SUBMITTER: Albro MB

PROVIDER: S-EPMC3810401 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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

Albro Michael B MB Nims Robert J RJ Cigan Alexander D AD Yeroushalmi Kevin J KJ Shim Jay J JJ Hung Clark T CT Ateshian Gerard A GA

Journal of biomechanics 20130327 8

A growing body of research has highlighted the role that mechanical forces play in the activation of latent TGF-β 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-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 motio ...[more]

PMID: 23540376

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Project description:Articular cartilage is integral to the mechanical function of many joints in the body. When injured, cartilage lacks the capacity to self-heal, and thus, therapies and replacements have been developed in recent decades to treat damaged cartilage. Given that the primary function of articular cartilage is mechanical in nature, rigorous physical evaluation of cartilage tissues undergoing treatment and cartilage constructs intended for replacement is an absolute necessity. With the large number of groups developing cartilage tissue engineering strategies, however, a variety of mechanical testing protocols have been reported in the literature. This lack of consensus in testing methods makes comparison between studies difficult at times, and can lead to misinterpretation of data relative to native tissue. Therefore, the purpose of this study was to systematically review mechanical testing of articular cartilage and cartilage repair constructs over the past 10 years (January 2009-December 2018), to highlight the most common testing configurations, and to identify key testing parameters. For the most common tests, key parameters identified in this systematic review were validated by characterizing both cartilage tissue and hydrogels commonly used in cartilage tissue engineering. Our findings show that compression testing was the most common test performed (80.2%; 158/197), followed by evaluation of frictional properties (18.8%; 37/197). Upon further review of those studies performing compression testing, the various modes (ramp, stress relaxation, creep, dynamic) and testing configurations (unconfined, confined, in situ) are described and systematically reviewed for parameters, including strain rate, equilibrium time, and maximum strain. This systematic analysis revealed considerable variability in testing methods. Our validation testing studies showed that such variations in testing criteria could have large implications on reported outcome parameters (e.g., modulus) and the interpretation of findings from these studies. This analysis is carried out for all common testing methods, followed by a discussion of less common trends and directions in the mechanical evaluation of cartilage tissues and constructs. Overall, this work may serve as a guide for cartilage tissue engineers seeking to rigorously evaluate the physical properties of their novel treatment strategies. Impact Statement Articular cartilage tissue engineering has made significant strides with regard to treatments and replacements for injured tissue. The evaluation of these approaches typically involves mechanical testing, yet the plethora of testing techniques makes comparisons between studies difficult, and often leads to misinterpretation of data compared with native tissue. This study serves as a guide for the mechanical testing of cartilage tissues and constructs, highlighting recent trends in test conditions and validating these common procedures. Cartilage tissue engineers, especially those unfamiliar with mechanical testing protocols, will benefit from this study in their quest to physically evaluate novel treatment and regeneration approaches.

Dataset Information

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

Publications

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

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