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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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Circadian Rhythms and Gene Regulation02:19

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Hormones and Bone Tissue01:17

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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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Skeleton and Calcium Homeostasis01:21

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Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
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Related Experiment Video

Updated: Mar 26, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
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Circadian Clock Regulates Bone Resorption in Mice.

Cheng Xu1,2,3, Hiroki Ochi1,2, Toru Fukuda1,2

  • 1Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|February 4, 2016
PubMed
Summary

The circadian clock regulates bone resorption via osteoclast Bmal1. This study reveals Bmal1 controls osteoclast differentiation and bone mass by interacting with SRC family proteins and regulating Nfatc1 transcription.

Keywords:
BMAL1CIRCADIAN CLOCKNFATC1SRCS FAMILY

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Area of Science:

  • * Molecular biology
  • * Chronobiology
  • * Bone biology

Background:

  • * The circadian clock regulates numerous physiological processes, and its dysfunction is linked to diseases like cancer and obesity.
  • * Clinical evidence indicates circadian rhythm influences bone resorption, but the underlying molecular mechanisms are unclear.
  • * Understanding circadian control of bone metabolism is crucial for treating bone-related disorders.

Purpose of the Study:

  • * To elucidate the molecular mechanism by which the circadian clock regulates bone resorption.
  • * To investigate the role of the circadian gene Bmal1 in osteoclast function and bone mass.
  • * To identify key molecular interactions involved in circadian regulation of bone resorption.

Main Methods:

  • * Generation and analysis of osteoclast-specific Bmal1-knockout mice.
  • * Cell-based assays to examine the transcriptional regulation of Nfatc1.
  • * Investigation of interactions between BMAL1:CLOCK and SRC family members.

Main Results:

  • * Osteoclast-specific Bmal1 knockout resulted in a high bone mass phenotype due to impaired osteoclast differentiation.
  • * BMAL1 was found to upregulate Nfatc1 transcription by binding to its promoter in conjunction with CLOCK.
  • * Steroid receptor coactivator (SRC) family members were identified as interacting partners that enhance BMAL1:CLOCK transcriptional activity.

Conclusions:

  • * Osteoclastic BMAL1 plays a critical role in controlling bone resorption.
  • * The mechanism involves BMAL1 interacting with SRC family proteins and binding to the Nfatc1 promoter.
  • * This provides novel insights into the molecular regulation of bone metabolism by the circadian clock.