title: Shearing of synovial fluid activates latent TGF-β.
abstract: OBJECTIVE
  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 joint function produces fluid shear, this study tested the hypothesis that the native latent TGF-β1 of synovial fluid can be activated by shearing.
  
  
  METHODS
  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.
  
  
  RESULTS
  Unsheared synovial fluid was found to contain high levels of latent TGF-β1 (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-β1 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-β1 at all times.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Mechanical Engineering, Columbia University, New York, NY 10027, United States.
authors.forename: M B
authors.initials: MB
authors.lastname: Albro
authors.forename: A D
authors.initials: AD
authors.lastname: Cigan
authors.forename: R J
authors.initials: RJ
authors.lastname: Nims
authors.forename: K J
authors.initials: KJ
authors.lastname: Yeroushalmi
authors.forename: S R
authors.initials: SR
authors.lastname: Oungoulian
authors.forename: C T
authors.initials: CT
authors.lastname: Hung
authors.forename: G A
authors.initials: GA
authors.lastname: Ateshian
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D006801:Humans; D008875:Middle Aged; D033081:Shear Strength / Q000502:physiology*; D013264:Stifle / Q000502:physiology*; D013314:Stress, Mechanical; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D016212:Transforming Growth Factor beta