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Ca2+ suppresses cell adhesion to osteopontin by attenuating binding affinity for integrin alpha v beta 3
1Department of Vascular Biology (VB-1), Scripps Research Institute, La Jolla, California 92037, USA.
The Journal of Biological Chemistry
|April 28, 1995
Summary
Osteopontin (OPN) binds to integrin alpha v beta 3, but calcium ions significantly reduce this binding. This suggests calcium modulates bone resorption by osteoclasts.
Area of Science:
- Biochemistry
- Cell Biology
- Bone Biology
Background:
- Osteopontin (OPN) is an extracellular matrix protein crucial for osteoclast adhesion to bone via integrin alpha v beta 3.
- OPN is unique among RGD-containing proteins for its high affinity to integrin alpha v beta 3 over platelet integrin alpha IIb beta 3.
Purpose of the Study:
- To investigate the binding characteristics of OPN to integrin alpha v beta 3.
- To determine the effect of physiological calcium levels on OPN-integrin binding and subsequent cell adhesion.
Main Methods:
- Recombinant human OPN (rOP27) and urinary OPN (uropontin) were used to measure binding to purified integrin alpha v beta 3.
- Surface plasmon resonance was employed to quantify binding constants in the presence of different divalent cations (Ca2+, Mn2+, Mg2+).
- RGD-dependent cell adhesion assays were performed.
Main Results:
- Both recombinant and urinary OPN bound to integrin alpha v beta 3 with similar affinities, supporting RGD-dependent cell adhesion.
- Physiological calcium levels markedly reduced the affinity of OPN for integrin alpha v beta 3 (26-fold lower in Ca2+ vs. Mn2+).
- The affinity of OPN for integrin alpha v beta 3 was significantly lower in Ca2+ compared to Mn2+ and Mg2+.
Conclusions:
- Osteopontin-integrin alpha v beta 3 binding and subsequent osteoclast adhesion are inhibited by physiological calcium concentrations.
- Elevated extracellular calcium, generated during bone resorption, may serve as a regulatory mechanism to modulate osteoclast activity and bone resorption.