Osteoclast differentiation and activation

  title={Osteoclast differentiation and activation},
  author={William J. Boyle and William S. Simonet and David L. Lacey},
Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the… 

Osteoclast Differentiation Assay.

A general protocol of inducing osteoclast differentiation from the murine macrophage cell line, RAW264.7, and identification of osteoclasts with the classical TRAP assay is described.

Identification of osteoclasts in culture.

Methods for the identification of osteoclasts formed in vitro are described and it is shown that RANKL and M-CSF can be induced from monocyte-macrophage lineage cells even in the absence of osteoblasts.

Generation of human osteoclasts from peripheral blood.

This chapter describes the method for generating human osteoclast from peripheral blood or buffy coats, as well as methods for studying both the differentiation and resorbing activity of these cells.

Osteoclast lineage and function.

Regulation of Osteoclast Activity

The stimulation of myelomonocytic precursors also requires MCSF to induce the formation of osteoclasts, and the aim of this chapter is to focus specifically on the regulation of osteoclast activity.

Osteoclasts: New Insights

New advances in the understanding of the mechanisms of osteoclast differentiation and function are discussed, including c-Fms and RANK signaling have been shown to regulate bone resorption by cross-talking with those activated by integrin αvβ3.

Generation and culture of osteoclasts.

The most commonly used procedures for the isolation, generation and characterization of human, rodent and chicken osteoclasts in vitro are summarized.

The role of osteoclast differentiation and function in skeletal homeostasis.

The importance of cell-cell contact and metabolic adaptation for differentiation, relatively overlooked aspects of osteoclast biology and biochemistry are focused on.



Bone resorption by osteoclasts.

Osteopetrotic mutants have provided a wealth of information about the genes that regulate the differentiation of osteoclasts and their capacity to resorb bone.

Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation

Regulation of the differentiation and function of osteoclasts

A hypothesis is presented in which the osteoclast is a mononuclear phagocyte directed towards a debriding function by TGF‐β, activated for this function by TRANCE, and induced to become specifically osteoclastic by the characteristics of the substrate or signals from bone cells that betoken such characteristics.

c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling.

Results identify Fos as a key regulator of osteoclast-macrophage lineage determination in vivo and provide insights into the molecular mechanisms underlying metabolic bone diseases.

Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL.

  • H. YasudaN. Shima T. Suda
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
A genetically engineered soluble form containing the extracellular domain of the protein induced OCL formation from spleen cells in the absence of osteoblasts/stromal cells, and it was concluded that the membrane-bound protein is osteoclast differentiation factor (ODF), a long-sought ligand mediating an essential signal to osteOClast progenitors for their differentiation into osteoclasts.

OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis

OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.

RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism.

  • J. LiI. Sarosi W. Boyle
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
Data indicate that RANK is the intrinsic cell surface determinant that mediates osteoprotegerin ligand effects on bone resorption and remodeling as well as the physiological and pathological effects of calciotropic hormones and proresorptive cytokines.

RANK is essential for osteoclast and lymph node development.

Investigating the physiological role of the TNF receptor (TNFR) family member, RANK, revealed that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation.

The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption

It is suggested that changes in but two downstream cytokines mediate the effects of large numbers of upstream hormones and cytokines suggests a regulatory mechanism for osteoclastogenesis of great efficiency and elegance.

Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function.

Findings suggest that OPG produced by osteoblasts/stromal cells is a physiologically important regulator in osteoclast differentiation and function and that RANKL expressed by osteobasts functions as a membrane-associated form.