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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

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

Summary

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

Related Experiment Videos

Last Updated: May 13, 2026

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

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

Published on: March 15, 2018

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.