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PMID: 20052601 Published · ppublish English Journal Article

Binding characteristics of the osteoarthritis-associated protein asporin.

Journal of bone and mineral metabolism ·Vol. 28 ·No. 4 ·2010-07-00 ·Pages 395-402

Kou I, Nakajima M, Ikegawa S

Abstract

Asporin is an extracellular matrix (ECM) protein that regulates cartilage matrix gene expression and cartilage formation by modulating the transforming growth factor-beta (TGF-beta) signaling pathway. Our previous studies have indicated that asporin binds to TGF-beta1 directly and inhibits TGF-beta1-mediated expression of cartilage matrix genes. However, it is still unknown how asporin interacts with TGF-beta1 and influences its activity. Using competition assays, we determined that amino acids 159-205 of asporin mediate its interaction with TGF-beta1 and effectively repress TGF-beta1-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-beta1. In contrast with previous in vivo findings, asporin did not affect the interaction between TGF-beta1 and the TGF-beta type II receptor (TbetaRII) 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-beta and TbetaRII in vitro. These findings suggest that asporin is one of the important cartilage matrix proteins that binds to the ECM and TGF-beta1 and thereby modulates interactions between TGF-beta and its signaling receptors.

MeSH Terms
Animals Cell Line Collagen Type II/genetics,metabolism Enzyme-Linked Immunosorbent Assay Extracellular Matrix Proteins/genetics,metabolism Mice Polymerase Chain Reaction Protein Binding Protein Serine-Threonine Kinases/genetics,metabolism Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta/genetics,metabolism Transforming Growth Factor beta/genetics,metabolism
Chemicals
Aspn protein, mouse Collagen Type II Extracellular Matrix Proteins Receptors, Transforming Growth Factor beta Transforming Growth Factor beta Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kou Ikuyo
Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nakajima Masahiro
Ikegawa Shiro
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Article Info
Journal
Journal of bone and mineral metabolism
Abbr.
J Bone Miner Metab
ISSN
1435-5604
DOI
10.1007/s00774-009-0145-8
Published
2010-07-00
Epub
2010-00-07
Pages
395-402
Language
English
Region
Japan
NLM ID
9436705
Subset
IM
External Links
PubMed source DOI: 10.1007/s00774-009-0145-8 View journal details
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