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Integrins and signaling in osteoclast function.

L T Duong1, P Lakkakorpi, I Nakamura

  • 1Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, PA 19486, USA. duong@merck.com

Matrix Biology : Journal of the International Society for Matrix Biology
|June 8, 2000
PubMed
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Osteoclasts use the alphavbeta3 integrin to bind bone matrix, which is crucial for bone resorption. This integrin activates signaling pathways and cytoskeletal changes essential for osteoclast function.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Integrin Signaling

Background:

  • Integrins are key adhesion receptors mediating cell-matrix and cell-cell interactions.
  • Osteoclasts, crucial for bone remodeling, highly express the alphavbeta3 integrin.
  • Alphavbeta3 integrin binds extracellular matrix proteins like vitronectin, osteopontin, and bone sialoprotein.

Purpose of the Study:

  • To investigate the role of alphavbeta3 integrin in osteoclast function and bone resorption.
  • To identify signaling and cytoskeletal molecules involved in alphavbeta3 integrin-dependent pathways in osteoclasts.

Main Methods:

  • Utilized RGD-containing peptides, RGD-mimetics, and alphavbeta3 blocking antibodies to inhibit bone resorption.
  • Investigated changes in cytosolic calcium levels in osteoclasts upon RGD-peptide treatment.

Related Experiment Videos

  • Examined the involvement of signaling molecules (e.g., PI3K, c-Src, PYK2, p130(cas)) and cytoskeletal proteins (e.g., paxillin, vinculin, gelsolin, F-actin).

    • Main Results:

    • Alphavbeta3 integrin plays a critical role in osteoclast function, as evidenced by inhibition of bone resorption by RGD-peptides and blocking antibodies.
    • RGD-containing peptides induce an increase in cytosolic calcium in osteoclasts.
    • Signaling molecules and cytoskeletal components are recruited to adhesion sites and the sealing zone of resorbing osteoclasts, indicating their involvement in integrin-mediated signaling and cell function.

    Conclusions:

    • The alphavbeta3 integrin is essential for osteoclast-mediated bone resorption.
    • Alphavbeta3 integrin signaling pathways involve phosphatidylinositol 3-kinase, c-Src, PYK2, and p130(cas).
    • Cytoskeletal elements like paxillin, vinculin, gelsolin, and F-actin are recruited to the sealing zone, linking adhesion to cytoskeletal organization and osteoclast activation for bone resorption.