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Related Concept Videos

Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

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Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
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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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Bone Formation by Intramembranous Ossification01:29

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Intramembranous ossification is one of the two processes involved in the development of bones within an embryo. The flat bones of the face, most of the cranial bones, and the clavicles are formed via this process. During intramembranous ossification, the bones develop directly from sheets of undifferentiated mesenchymal connective tissue.
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Osteoclasts in Bone Remodeling01:31

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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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Growth of Cartilage and Bone Tissue01:27

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Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
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Related Experiment Video

Updated: Aug 9, 2025

Culturing and Measuring Fetal and Newborn Murine Long Bones
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Endothelial-to-osteoblast transition in normal mouse bone development.

Song-Chang Lin1, Guoyu Yu1, Yu-Chen Lee1

  • 1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Iscience
|February 17, 2023
PubMed
Summary
This summary is machine-generated.

Endothelial cells (ECs) can transform into bone-forming osteoblasts (OSBs) during normal bone development. This EC-to-OSB transition offers a new perspective on how bone cells originate.

Keywords:
Biological sciencesCancerCell biology

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Bone Biology

Background:

  • Metastatic prostate cancer (PCa) in bone is associated with bone-forming lesions.
  • Previously, we demonstrated that PCa-induced bone arises from endothelial cells (ECs) undergoing EC-to-osteoblast (OSB) transition.

Purpose of the Study:

  • To investigate if EC-to-OSB transition occurs during normal bone formation.
  • To explore the cellular mechanisms underlying this transition.

Main Methods:

  • Development of a dual-color reporter mouse model (DRM) to track EC-OSB hybrid cells.
  • Observation of EC-to-OSB transition in embryonic and adult bone formation (endochondral and intramembranous).
  • In vitro studies using bone marrow- and lung-derived ECs cultured in osteogenic medium.
  • RNA-sequencing of EC-OSB hybrid cells and gene knockdown experiments (GATA3).

Main Results:

  • EC-to-OSB transition (co-expression of red and green fluorescent proteins) was observed in both endochondral and intramembranous bone formation.
  • Isolated ECs from DRM confirmed co-expression.
  • Bone marrow- and lung-derived ECs transitioned to OSBs and exhibited mineralization in vitro.
  • GATA family transcription factors, including GATA3, were upregulated in EC-OSB hybrid cells; GATA3 knockdown inhibited BMP4-induced mineralization.

Conclusions:

  • EC-to-OSB transition is a fundamental process in normal bone development.
  • This finding challenges existing paradigms and suggests an endothelial origin for osteoblasts.
  • The study identifies GATA transcription factors as key regulators in EC-to-OSB differentiation and mineralization.