Recent advances in understanding the mechanisms of osteoclast precursor fusion

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Bone marrow macrophages fuse on the bone surface to form multinucleated osteoclasts that then organize to efficiently resorb bone. Many, if not all, of the stages of macrophage fusion involve cytoskeletal components that reorganize the cells. Recruitment may involve chemotactic responses to bone matrix protein and calcium ion gradients and/or chemokine production by bone forming osteoblasts. The roles of integrins vary, depending on the particular subunits with some interfering with fusion and others having a participatory role. RANKL is essential for fusion and many identified modulators of fusion influence RANKL signaling pathways. Tetraspanins have been implicated in fusion of macrophages and myoblasts, but differences in impacts exist between these two cell types. Macrophage recruitment to apoptotic cells prior to their engulfment is driven by the exposed phospholipids on the external surface of the apoptotic cells and there is evidence that this same identification mechanism is employed in macrophage fusion. Because loss of cadherin or ADAM family members suppresses macrophage fusion, a crucial role for these membrane glycoproteins is evident. The Ig membrane glycoprotein superfamily members CD200 and MFR/ SIRPa are involved in macrophage fusion, although their influences are unresolved. Differential screenings have identified the structurally related membrane proteins DC-STAMP and OC-STAMP as required components for fusion and the contributions to fusion remain active areas of investigation. While many of the key components involved in these processes have been identified, a great deal of work remains in resolving the precise processes involved and the interactions between key contributors to multinucleated osteoclast formation.

Original languageEnglish (US)
Pages (from-to)1058-1062
Number of pages5
JournalJournal of Cellular Biochemistry
Volume110
Issue number5
DOIs
StatePublished - Aug 1 2010

Fingerprint

Osteoclasts
Macrophages
Fusion reactions
Bone
Membrane Glycoproteins
Bone and Bones
Tetraspanins
Bone Matrix
Myoblasts
Cellular Structures
Cadherins
Cells
Osteoblasts
Chemokines
Integrins
Phospholipids
Membrane Proteins
Bone Marrow
Electric fuses
Ions

Keywords

  • CD200
  • DC-Stamp
  • Fusion
  • Macrophage
  • MFR/SIRPα
  • OC-Stamp
  • Osteoclasts

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Recent advances in understanding the mechanisms of osteoclast precursor fusion. / Oursler, Merry Jo.

In: Journal of Cellular Biochemistry, Vol. 110, No. 5, 01.08.2010, p. 1058-1062.

Research output: Contribution to journalArticle

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