Related Experiment Video
Updated: May 29, 2026
11:52
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
Lineage-committed osteoclast precursors circulate in blood and settle down into bone
Akinori Muto1, Toshihide Mizoguchi, Nobuyuki Udagawa
1Institute for Oral Science, Matsumoto Dental University, Nagano, Japan.
Summary
Quiescent osteoclast precursors (QOPs) circulate in the blood, identified by receptor activator of NF-κB (RANK). These RANK-positive cells settle in bone, differentiating into osteoclasts and offering new insights into bone remodeling.
Area of Science:
- Cell Biology
- Immunology
- Bone Biology
Background:
- Osteoclasts, crucial for bone resorption, originate from the monocyte/macrophage lineage.
- The identity and characteristics of circulating osteoclast precursors remain largely unknown.
- Previous work identified cell cycle-arrested quiescent osteoclast precursors (QOPs) on bone surfaces.
Purpose of the Study:
- To identify and characterize circulating osteoclast precursors.
- To investigate the role of receptor activator of NF-κB (RANK)-positive cells in osteoclast formation.
- To determine the origin and behavior of QOPs in vivo.
Main Methods:
- Isolation and characterization of receptor activator of NF-κB (RANK)-positive cells from mouse bone marrow and peripheral blood.
- Assessment of cell proliferation, phagocytosis, and differentiation potential.
- In vivo studies using bromodeoxyuridine labeling and implantation of bone morphogenetic protein-2 (BMP)-containing disks.
- Analysis of RANK-positive cell behavior in RANK ligand-deficient mice and following FYT720 administration.
Main Results:
- RANK-positive cells from bone marrow and blood exhibit QOP characteristics, expressing c-Fms but not other monocyte/granulocyte markers.
- These cells are non-phagocytic, non-proliferative, and differentiate into osteoclasts but not dendritic cells.
- In vivo, most newly formed osteoclasts in ectopic bone were bromodeoxyuridine-negative, indicating a quiescent origin.
- RANK-positive cells in circulation have a slower proliferation rate and longer lifespan than macrophages.
- FYT720 administration increased the presence of RANK-positive cells in the bloodstream, suggesting enhanced egress from hematopoietic tissues.
Conclusions:
- Lineage-determined quiescent osteoclast precursors (QOPs) circulate in the blood.
- These RANK-positive circulating cells possess the characteristics of osteoclast precursors and home to bone.
- Understanding circulating QOPs provides novel insights into bone remodeling and potential therapeutic targets.
Related Concept Videos
01:21Lineage Commitment
Commitment is the process whereby stem cells:
01:30Bone Cells and Tissue
Bones contain a relatively small number of cells entrenched in a matrix of organic and inorganic components. Although bone cells compose only a small amount of the bone volume, they are crucial to its function. Four types of cells are found within the bone tissue— osteoblasts, osteocytes, osteogenic cells, and osteoclasts.
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the periosteum and...
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the periosteum and...
01:31Osteoclasts 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...
01:40Bone 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.
01:21Hematopoiesis
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
01:34Production of Formed Elements
Hemangioblasts are multipotent stem cells originating from the mesoderm. They give rise to hematopoietic stem cells (HSCs), which undergo hematopoiesis to produce all the formed elements of blood. This process is regulated by a complex network of hematopoietic growth factors, including transcription factors, growth factors, and cytokines. These factors stimulate the HSCs to divide and differentiate, though some HSCs remain undifferentiated to maintain a self-renewing pool.
Most HSCs commit to...
Most HSCs commit to...