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Shearing of synovial fluid activates latent TGF-?.

ABSTRACT: TGF-? is synthesized in an inactive latent complex that is unable to bind to membrane receptors, thus unable to induce a cellular biological response until it has been activated. In addition to activation by chemical mediators, recent studies have demonstrated that mechanical forces may activate latent TGF-?via integrin-mediated cellular contractions, or mechanical shearing of blood serum. Since TGF-? is present in synovial fluid in latent form, and since normal diarthrodial joint function produces fluid shear, this study tested the hypothesis that the native latent TGF-?1 of synovial fluid can be activated by shearing.Synovial fluid from 26 bovine joints and three adult human joints was sheared at mean shear rates up to 4000 s(-1) for up to 15 h.Unsheared synovial fluid was found to contain high levels of latent TGF-?1 (4.35 ± 2.02 ng/mL bovine, 1.84 ± 0.89 ng/mL human; mean ± radius of 95% confidence interval) and low amounts (<0.05 ng/mL) of the active peptide. Synovial fluid concentrations of active TGF-?1 increased monotonically with shear rate and shearing duration, reaching levels of 2.64 ± 1.22 ng/mL for bovine and 0.60 ± 0.39 ng/mL for human synovial fluid. Following termination of shearing, there was no statistical change in these active levels over the next 8 h for either species, demonstrating long-term stability of the activated peptide. The unsheared control group continued to exhibit negligible levels of active TGF-?1 at all times.Results confirmed the hypothesis of this study and suggest that shearing of synovial fluid might contribute an additional biosynthetic effect of mechanical loading of diarthrodial joints.

SUBMITTER: Albro MB

PROVIDER: S-EPMC3448789 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Shearing of synovial fluid activates latent TGF-β.

Albro M B MB Cigan A D AD Nims R J RJ Yeroushalmi K J KJ Oungoulian S R SR Hung C T CT Ateshian G A GA

Osteoarthritis and cartilage 20120731 11

<h4>Objective</h4>TGF-β is synthesized in an inactive latent complex that is unable to bind to membrane receptors, thus unable to induce a cellular biological response until it has been activated. In addition to activation by chemical mediators, recent studies have demonstrated that mechanical forces may activate latent TGF-βvia integrin-mediated cellular contractions, or mechanical shearing of blood serum. Since TGF-β is present in synovial fluid in latent form, and since normal diarthrodial jo ...[more]

PMID: 22858668

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Shearing of synovial fluid activates latent TGF-?.

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Shearing of synovial fluid activates latent TGF-β.

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