Activin A is an anticatabolic autocrine cytokine in articular cartilage whose production is controlled by fibroblast growth factor 2 and NF-kappaB

Arthritis Rheum. 2007 Nov;56(11):3715-25. doi: 10.1002/art.22953.


Objective: Proteomic analysis has previously shown that activin A, a member of the transforming growth factor beta family, is produced by human articular cartilage. This study was undertaken to investigate whether activin A affects cartilage matrix catabolism and how its production is regulated.

Methods: The effect of exogenous activin A on interleukin-1-induced aggrecanase-generated neoepitope production was assessed by Western blotting, using medium from human cartilage explants. Levels of activin A production were determined by enzyme-linked immunosorbent assay. For genes of interest, messenger RNA (mRNA) induction in cartilage explants or primary chondrocyte monolayers was assessed by reverse transcriptase-polymerase chain reaction. Activin A activity in cartilage explant medium was measured by incubating it with human dermal fibroblasts and determining the increase in phospho-Smad2 by Western blotting.

Results: Activin A (1-10 ng/ml) suppressed aggrecanase-mediated cleavage of aggrecan in human articular cartilage. Activin A mRNA and protein secretion were induced by dissection and culture of human or porcine articular cartilage. This activin A was biologically active. Its production was due to an active cellular process and was enhanced in osteoarthritic (OA) tissue. Activin A production on dissection was reduced by 80% by the fibroblast growth factor (FGF) receptor inhibitor PD173074 and by 70% by the IKK inhibitor BMS345541.

Conclusion: Activin A is potentially an anticatabolic molecule in articular cartilage. Its expression is induced by wounding in an FGF-2- and NF-kappaB-dependent manner. OA cartilage produced more activin A than did normal cartilage in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / metabolism*
  • Activins / pharmacology
  • Aggrecans / metabolism
  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Endopeptidases / metabolism
  • Fibroblast Growth Factor 2 / metabolism*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Imidazoles / pharmacology
  • NF-kappa B / metabolism*
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / pathology
  • Pyrimidines / pharmacology
  • Quinoxalines / pharmacology
  • Smad2 Protein / metabolism
  • Sus scrofa


  • 4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline
  • Aggrecans
  • Cytokines
  • Imidazoles
  • NF-kappa B
  • PD 173074
  • Pyrimidines
  • Quinoxalines
  • SMAD2 protein, human
  • Smad2 Protein
  • activin A
  • Fibroblast Growth Factor 2
  • Activins
  • Endopeptidases
  • aggrecanase