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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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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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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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A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
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Related Experiment Video

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Osteoclast Derivation from Mouse Bone Marrow
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[Role of mitochondria in osteoclast function].

Tsuyoshi Miyazaki1

  • 1Department of Geriatric Medicine and Orthopaedic Surgery, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Japan.

Clinical Calcium
|October 29, 2013
PubMed
Summary

Mitochondria regulate osteoclast function by controlling energy levels. Tfam deficiency in osteoclasts causes ATP depletion, increasing bone resorption and apoptosis, revealing a novel feedback loop for bone remodeling.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Bone Biology

Background:

  • Mitochondria are vital organelles generating ATP for cellular energy.
  • Osteoclasts are specialized bone-resorbing cells with high energy demands.
  • Osteoclast survival and bone resorption capacity present a biological paradox.

Purpose of the Study:

  • To elucidate the role of mitochondria in osteoclast function.
  • To investigate the impact of mitochondrial dysfunction on osteoclast activity.
  • To explore the relationship between ATP levels and osteoclast behavior.

Main Methods:

  • Mitochondrial transcription factor A (Tfam) deficiency model in osteoclasts.
  • Assessment of ATP levels, apoptosis, and bone-resorbing activity.

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  • Analysis of autocrine/paracrine ATP signaling pathways.

    • Main Results:

    • Tfam deficiency led to significant ATP depletion in osteoclasts.
    • ATP depletion correlated with increased bone-resorbing activity and accelerated apoptosis.
    • Endogenous ATP was identified as a negative regulator of osteoclast function via feedback loops.

    Conclusions:

    • Mitochondria play a critical role in balancing osteoclast survival and bone resorption.
    • A novel mechanism involving ATP depletion and feedback regulation by endogenous ATP governs osteoclast function.
    • These findings offer new insights into the regulation of bone remodeling and potential therapeutic targets.