Related Experiment Video

Updated: May 13, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

Zap70 inhibits Syk-mediated osteoclast function

Wei Zou1, Monica Croke, Tomohiro Fukunaga

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Journal of Cellular Biochemistry
|March 16, 2013
PubMed

Insights

Zap70 cannot replace Syk in osteoclasts (OCs), failing to restore normal cell function. Instead, Zap70 inhibits wild-type OC cytoskeletal organization and bone resorption, highlighting Syk

Area of Science:

  • Cell Biology
  • Biochemistry
  • Immunology

Background:

  • Osteoclast (OC) differentiation and resorptive capacity are regulated by αvβ3 integrin signaling, involving the tyrosine kinase Syk.
  • Syk-deficient OCs exhibit impaired cytoskeletal organization, including failure to spread and form actin rings.
  • The Syk family includes Syk and Zap70; Zap70's structural similarity and compensatory roles in other cells prompted investigation into its function in OCs.

Purpose of the Study:

  • To determine if Zap70 can functionally substitute for Syk in osteoclasts.
  • To investigate the inhibitory role of Zap70 on wild-type osteoclast function.

Main Methods:

  • Expression of Syk or Zap70 in Syk-deficient (Syk(-/-)) osteoclasts.
  • Assessment of osteoclast spreading, actin ring formation, and bone resorptive activity.
  • Analysis of αvβ3 integrin-induced SLP76 phosphorylation and activation of Syk and Vav3.

Main Results:

  • Syk expression restored normal cytoskeletal organization and αvβ3 integrin-induced SLP76 phosphorylation in Syk(-/-) OCs.
  • Zap70 expression failed to rescue the cytoskeletal defects in Syk(-/-) OCs and did not rescue SLP76 phosphorylation.
  • Zap70 expression inhibited wild-type OC spreading, actin ring formation, bone resorption, and blocked integrin-activated Syk, Vav3, and SLP76 phosphorylation in a kinase-dependent manner.

Conclusions:

  • Zap70 cannot compensate for the absence of Syk in osteoclast cytoskeletal organization and function.
  • Zap70 actively inhibits osteoclast cytoskeletal organization and bone resorptive activity, independent of differentiation.
  • The kinase domain of Syk is essential for OC function, whereas Zap70's kinase activity is inhibitory.

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