Chondroitin Sulfate-E Binds to Both Osteoactivin and Integrin αvβ3 and Inhibits Osteoclast Differentiation

Tatsuya Miyazaki, Satoshi Miyauchi, Takahisa Anada, Akira Tawada, Osamu Suzuki

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Integrins and their ligands have been suggested to be associated with osteoclast-mediated bone resorption. The present study was designed to investigate whether chondroitin sulfate E (CS-E), which is one of the sulfated glycosaminoglycans (GAGs), is involved in osteoactivin (OA) activity, and osteoclast differentiation. The binding affinity of sulfated GAGs to integrin and its ligand was measured using biotin-labeled CS-E, and the osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase staining and a pit formation assay. CS-E as well as CS-B, synthetic chondroitin polysulfate, and heparin inhibited osteoclast differentiation of bone marrow-derived macrophages. Pre-coating of OA to synthetic calcium phosphate-coated plates enhanced the osteoclastic differentiation of RAW264 cells, and addition of a neutralizing antibody to OA inhibited its differentiation. CS-E bound not only to OA, fibronectin, and vitronectin, but also to its receptor integrin αVβ3, and inhibited the direct binding of OA to integrin αVβ3. Furthermore, CS-E blocked the binding of OA to cells and inhibited OA-induced osteoclastic differentiation. On the other hand, heparinase treatment of RAW264 cells inhibited osteoclastic differentiation. Since binding of OA to the cells was inhibited by the presence of heparan sulfate or heparinase treatment of cells, heparan sulfate proteoglycan (HSPG) was also considered to be an OA receptor. Taken together, the present results suggest that CS-E is capable of inhibiting OA-induced osteoclast differentiation by blocking the interaction of OA to integrin αVβ3 and HSPG. J. Cell. Biochem. 116: 2247-2257, 2015.

Original languageEnglish
Pages (from-to)2247-2257
Number of pages11
JournalJournal of Cellular Biochemistry
Volume116
Issue number10
DOIs
Publication statusPublished - Oct 1 2015
Externally publishedYes

Fingerprint

Chondroitin Sulfates
Osteoclasts
Integrins
A73025
Heparin Lyase
Heparan Sulfate Proteoglycans
Bone
Chondroitin
Ligands
Vitronectin
Heparitin Sulfate
Macrophages
Bone Resorption
Biotin
Acid Phosphatase
Neutralizing Antibodies
Fibronectins
Heparin
Cell Differentiation
Assays

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chondroitin Sulfate-E Binds to Both Osteoactivin and Integrin αvβ3 and Inhibits Osteoclast Differentiation. / Miyazaki, Tatsuya; Miyauchi, Satoshi; Anada, Takahisa; Tawada, Akira; Suzuki, Osamu.

In: Journal of Cellular Biochemistry, Vol. 116, No. 10, 01.10.2015, p. 2247-2257.

Research output: Contribution to journalArticle

Miyazaki, Tatsuya ; Miyauchi, Satoshi ; Anada, Takahisa ; Tawada, Akira ; Suzuki, Osamu. / Chondroitin Sulfate-E Binds to Both Osteoactivin and Integrin αvβ3 and Inhibits Osteoclast Differentiation. In: Journal of Cellular Biochemistry. 2015 ; Vol. 116, No. 10. pp. 2247-2257.
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