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Related Concept Videos

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...
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
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...
Hormones and Bone Tissue01:17

Hormones and Bone Tissue

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

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...
Role of Vitamins in Maintaining Bone Health01:25

Role of Vitamins in Maintaining Bone Health

The growth and maintenance of bone are regulated by a combination of nutritional factors, including vitamins, such as vitamin A, B12, C, D, and K.
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Bim, Bak, and Bax regulate osteoblast survival.

Min Liang1, Graham Russell, Philippa A Hulley

  • 1Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford, United Kingdom.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|February 7, 2008
PubMed
Summary

Osteoblasts undergo apoptosis when growth factors are limited, mediated by Bim, Bak, and Bax proteins. Targeting Bim regulation may enhance osteoblast survival.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteoblasts require continuous prosurvival signals from their microenvironment.
  • Trophic factor deprivation triggers osteoblast apoptosis.
  • This study investigates the roles of Bim, Bak, and Bax in this apoptotic process.

Purpose of the Study:

  • To establish the regulation of Bim, Bak, and Bax in osteoblast apoptosis.
  • To determine the functional role of these proteins in response to growth factor withdrawal.
  • To identify potential therapeutic targets for enhancing osteoblast viability.

Main Methods:

  • Utilized MBA-15.4 murine osteoblasts and primary human bone marrow stromal cells (hBMSCs).
  • Induced apoptosis via serum starvation (growth factor depletion).
  • Quantified protein and gene expression, assessed apoptosis using siRNA and TUNEL staining, and analyzed mitochondrial potential.

Main Results:

  • Serum depletion upregulated the proapoptotic protein Bim transcriptionally, preceding caspase 3 activation and apoptosis.
  • Prosurvival kinase (ERK, PKB) dephosphorylation preceded Bim upregulation.
  • Knockdown of Bim, Bak, or Bax significantly reduced osteoblast apoptosis, with Bax and Bak playing a major role.

Conclusions:

  • Bim, Bak, and Bax are key mediators of trophic factor withdrawal-induced osteoblast apoptosis.
  • The upstream regulation of Bim presents potential therapeutic targets for improving osteoblast survival.