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Related Concept Videos

Bone Disorders01:29

Bone Disorders

Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
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Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
The Functions of the Skeletal System01:22

The Functions of the Skeletal System

The most apparent functions of the skeletal system are support, protection, and movement. However, bone tissue also performs several other critical metabolic functions. For one, the bone matrix acts as a reservoir for a number of minerals important to the functioning of the body, especially calcium and phosphorus. These minerals, present in the bone tissue, can be released back into the bloodstream when required. Calcium ions, for example, are essential for muscle contractions and controlling...
Anaphase Promoting Complex00:50

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Cytoskeletal Accessory Proteins

The cytoskeleton is an essential cell component that plays several structural and functional roles. However, the filaments that make up the cytoskeleton cannot function independently and depend on the accessory or ancillary proteins to effectively carry out their function. Accessory proteins associate with cytoskeletal filaments and their monomers, aiding filament formation and function. They also help in the cross-communication among cytoskeletal filaments. Cytoskeletal accessory proteins are...

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Related Experiment Video

Updated: Jun 10, 2026

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts.

Wei Zou1, Tingting Zhu, Clarissa S Craft

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

Journal of Cell Science
|August 20, 2010
PubMed
Summary
This summary is machine-generated.

DAP12 deficiency in osteoclasts impairs their cytoskeleton, hindering bone resorption. FcRgamma partially rescues this defect, suggesting cytoskeletal dysfunction is the primary issue, not impaired differentiation.

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Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
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Published on: March 15, 2018

Area of Science:

  • Immunology
  • Cell Biology
  • Skeletal Biology

Background:

  • DAP12 (DNAX-activating protein 12) is an ITAM-bearing protein involved in osteoclast function.
  • Mice lacking DAP12 show mild osteopetrosis, but severe osteopetrosis in mice lacking both DAP12 and FcRgamma suggests FcRgamma compensation.

Purpose of the Study:

  • To investigate whether DAP12 deficiency primarily affects osteoclast differentiation or bone resorption capacity.
  • To determine the role of FcRgamma, specifically OSCAR, in compensating for DAP12 deficiency in osteoclasts.

Main Methods:

  • Osteoclast differentiation and functional assays were performed on wild-type and Dap12(-/-) mice.
  • Overexpression of OSCAR fused to FLAG (OSCAR-FLAG) in Dap12(-/-) osteoclasts.
  • Assessment of osteoclast cytoskeleton, transmigration, and bone resorption capacity.

Main Results:

  • Dap12(-/-) osteoclasts exhibit normal differentiation but possess a dysfunctional cytoskeleton, impairing transmigration and bone resorption.
  • OSCAR-FLAG partially rescued the cytoskeletal defect in Dap12(-/-) osteoclasts cultured on bone, but not on osteoblasts.
  • Osteoblasts did not normalize Dap12(-/-) osteoclasts, indicating a lack of relevant OSCAR ligand in these cells.

Conclusions:

  • Cytoskeletal dysfunction, not impaired differentiation, is the primary consequence of DAP12 deficiency in osteoclasts.
  • FcRgamma, via OSCAR, plays a partial compensatory role in osteoclast function when DAP12 is absent.
  • Bone-forming cells do not appear to provide sufficient OSCAR ligand to rescue DAP12-deficient osteoclast function.