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Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

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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...
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Bone Remodeling01:40

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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.
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Histone Modification02:32

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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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Hormones and Bone Tissue01:17

Hormones and Bone Tissue

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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...
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Bone Disorders01:29

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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.
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Histone deacetylases (HDAC) in physiological and pathological bone remodelling.

M D Cantley1, A C W Zannettino2, P M Bartold3

  • 1Discipline of Physiology, School of Medicine, University of Adelaide, SA 5005, Australia; Myeloma Research Laboratory, Cancer Theme, SAHMRI, Adelaide, SA 5000, Australia; Colgate Australian Clinical Dental Research Centre, Adelaide Dental School, University of Adelaide, SA 5005, Australia.

Bone
|December 4, 2016
PubMed
Summary

Histone deacetylase inhibitors (HDACi) targeting specific enzymes offer new hope for treating bone loss diseases. Understanding individual HDAC isozymes is key to developing effective therapies with fewer side effects.

Keywords:
Histone deacetylases (HDAC)Myeloma bone diseaseOsteoblastsOsteoclastsPeriodontitisRheumatoid arthritis

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Epigenetics

Background:

  • Histone deacetylases (HDACs) regulate gene expression epigenetically.
  • HDAC inhibitors (HDACi) are clinically used for malignancies.
  • HDACs are increasingly recognized for roles in non-malignant conditions like bone loss.

Purpose of the Study:

  • To review the roles of individual HDAC isozymes in bone cells.
  • To examine the effects of HDAC inhibitors on bone remodeling in pathological bone loss.
  • To highlight the potential of isozyme-specific HDACi for treating bone diseases.

Main Methods:

  • Literature review of HDAC isozyme functions.
  • Analysis of HDAC inhibitor effects on osteoblasts, osteoclasts, and osteocytes.
  • Examination of HDAC roles in periodontitis, rheumatoid arthritis, and myeloma bone disease.

Main Results:

  • HDACs play critical roles in regulating bone cell function and bone remodeling.
  • HDAC inhibitors demonstrate potential in preclinical models of bone loss.
  • Isozyme-specific HDAC inhibitors are crucial for understanding individual HDAC functions and developing targeted therapies.

Conclusions:

  • Targeting specific HDAC isozymes holds promise for treating pathological bone loss.
  • Isozyme-specific HDAC inhibitors may offer improved efficacy and reduced side effects compared to broad-spectrum inhibitors.
  • Further research into individual HDAC functions is essential for advancing bone disease therapeutics.