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Binding characteristics of the osteoarthritis-associated protein asporin

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Abstract

Asporin is an extracellular matrix (ECM) protein that regulates cartilage matrix gene expression and cartilage formation by modulating the transforming growth factor-β (TGF-β) signaling pathway. Our previous studies have indicated that asporin binds to TGF-β1 directly and inhibits TGF-β1-mediated expression of cartilage matrix genes. However, it is still unknown how asporin interacts with TGF-β1 and influences its activity. Using competition assays, we determined that amino acids 159–205 of asporin mediate its interaction with TGF-β1 and effectively repress TGF-β1-induced cartilage matrix gene expression. Asporin also has a binding ability to type II collagen in vitro, but its binding pattern is different from that of TGF-β1. In contrast with previous in vivo findings, asporin did not affect the interaction between TGF-β1 and the TGF-β type II receptor (TβRII) by itself or in the presence of type II collagen in vitro. However, in the presence of heparin/heparan sulfate, asporin inhibits the interaction between TGF-β and TβRII in vitro. These findings suggest that asporin is one of the important cartilage matrix proteins that binds to the ECM and TGF-β1 and thereby modulates interactions between TGF-β and its signaling receptors.

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Acknowledgments

We thank Hideki Kizawa for help in the study and Tomomi Isono and Tomoko Kusadokoro for excellent technical assistance.

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Authors and Affiliations

  1. Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Ikuyo Kou, Masahiro Nakajima & Shiro Ikegawa

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  1. Ikuyo Kou
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  2. Masahiro Nakajima
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  3. Shiro Ikegawa
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Correspondence to Shiro Ikegawa.

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Kou, I., Nakajima, M. & Ikegawa, S. Binding characteristics of the osteoarthritis-associated protein asporin. J Bone Miner Metab 28, 395–402 (2010). https://doi.org/10.1007/s00774-009-0145-8

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  • DOI: https://doi.org/10.1007/s00774-009-0145-8

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