Related Experiment Video

Updated: Jun 18, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Regulation of osteoclast apoptosis by Bcl-2 family protein Bim and Caspase-3

Sakae Tanaka1, Hidetoshi Wakeyama, Toru Akiyama

  • 1Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. tanakas-ort@h.u-tokyo.ac.jp

Advances in Experimental Medicine and Biology
|December 2, 2009
PubMed

Insights

The Caspase-3-Bim axis is crucial for osteoclast apoptosis and activity. Inhibiting Caspase-3 in osteoclasts leads to shorter lifespan and increased bone resorption.

Area of Science:

  • Cell biology
  • Bone biology
  • Apoptosis regulation

Background:

  • Osteoclasts are critical for bone remodeling.
  • The Bcl-2 family protein Bim regulates osteoclast apoptosis.
  • Caspase-3 plays a role in the degradation of Bim.

Purpose of the Study:

  • To investigate the role of the Caspase-3-Bim axis in osteoclast apoptosis and function.
  • To determine the impact of Caspase-3 deficiency on osteoclast lifespan and activity.

Main Methods:

  • Utilized caspase-3 knockout (caspase-3 -/-) mice.
  • Generated and analyzed osteoclasts from wild-type and caspase-3 -/- littermates.
  • Assessed osteoclast lifespan and bone-resorbing activity.

Main Results:

  • Osteoclasts lacking Caspase-3 (caspase-3 -/-) showed a significantly shorter lifespan compared to wild-type osteoclasts.
  • Osteoclasts from caspase-3 -/- mice exhibited increased bone-resorbing activity.
  • Bim degradation, a key event in apoptosis, is regulated by Caspase-3.

Conclusions:

  • The Caspase-3-Bim axis is a key regulator of both osteoclast apoptosis and activation.
  • Caspase-3 deficiency impairs osteoclast apoptosis, leading to heightened bone resorption.
  • Targeting the Caspase-3-Bim pathway may offer therapeutic strategies for bone diseases.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

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...