Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

Author:

Yamada Jun1,Tsuji Kunikazu23ORCID,Miyatake Kazumasa1ORCID,Matsukura Yu1ORCID,Abula Kahaer1,Inoue Makiko4,Sekiya Ichiro5,Muneta Takeshi123

Affiliation:

1. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan

2. Department of Cartilage Regeneration, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

3. International Research Center for Molecular Science in Tooth and Bone Diseases (Global Center of Excellence Program), Tokyo Medical and Dental University, Tokyo 113-8519, Japan

4. Department of Plastic and Reconstructive Surgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan

5. Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan

Abstract

Activins are proinflammatory cytokines which belong to the TGFβsuperfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.

Funder

Japan Society for the Promotion of Science

Publisher

Hindawi Limited

Subject

Immunology and Allergy

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