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Arthritis Rheum. 2007 Nov;56(11):3715-25.

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

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1
Kennedy Institute of Rheumatology, Imperial College London, London, UK.

Abstract

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.

PMID:
17968943
DOI:
10.1002/art.22953
[Indexed for MEDLINE]
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