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Updated: May 27, 2026
06:17
Osteoclast Derivation from Mouse Bone Marrow
Published on: November 6, 2014
Rac deletion in osteoclasts causes severe osteopetrosis
Monica Croke1, F Patrick Ross, Matti Korhonen
1Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Journal of Cell Science
|November 25, 2011
Summary
Rac GTPases are crucial for bone resorption by regulating osteoclast function. Combined deficiency in Rac1 and Rac2 impairs osteoclast cytoskeleton organization, leading to severe osteopetrosis due to functional defects, not differentiation arrest.
Area of Science:
- Cell Biology
- Skeletal Biology
- Molecular Biology
Background:
- Cdc42 is known to stimulate osteoclastogenesis and bone resorption.
- The role of its related GTPase, Rac, in osteoclast function remains largely unknown.
Purpose of the Study:
- To investigate the impact of Rac GTPases on osteoclast function and bone resorption.
- To elucidate the specific mechanisms by which Rac GTPases influence osteoclast activity.
Main Methods:
- Generation of Rac1 and Rac2 single and double knockout (RacDKO) mouse models.
- Analysis of osteoclast differentiation, function, and cytoskeleton organization in knockout models.
- Assessment of bone resorption and osteopetrosis in vivo.
Main Results:
- Deletion of Rac1 or Rac2 alone had no effect on bone resorption.
- Combined deficiency of Rac1 and Rac2 (RacDKO) resulted in severe osteopetrosis.
- RacDKO osteoclasts showed impaired bone resorption due to failed cytoskeleton organization (actin rings, ruffled borders) and reduced motility, despite normal differentiation.
- Abnormal Arp3 distribution was observed in RacDKO osteoclasts.
Conclusions:
- Rac1 and Rac2 are mutually compensatory and essential for osteoclast cytoskeleton organization and function.
- Combined Rac1 and Rac2 deficiency impairs osteoclast resorptive capacity, leading to osteopetrosis.
- Rac GTPases regulate osteoclast cytoskeleton organization, distinct from their role in differentiation.
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