Regulation of osteoclasts by membrane-derived lipid mediators

Tsukasa Oikawa, Yukiko Kuroda, Koichi Matsuo

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

Osteoclasts are bone-resorbing cells of monocytic origin. An imbalance between bone formation and resorption can lead to osteoporosis or osteopetrosis. Osteoclastogenesis is triggered by RANKL- and IP3-induced Ca2+ influx followed by activation of NFATc1, a master transcription factor for osteoclastogenic gene regulation. During differentiation, osteoclasts undergo cytoskeletal remodeling to migrate and attach to the bone surface. Simultaneously, they fuse with each other to form multinucleated cells. These processes require PI3-kinase-dependent cytoskeletal protein activation to initiate cytoskeletal remodeling, resulting in the formation of circumferential podosomes and fusion-competent protrusions. In multinucleated osteoclasts, circumferential podosomes mature into stabilized actin rings, which enables the formation of a ruffled border where intensive membrane trafficking is executed. Membrane lipids, especially phosphoinositides, are key signaling molecules that regulate osteoclast morphology and act as second messengers and docking sites for multiple important effectors. We examine the critical roles of phosphoinositides in the signaling cascades that regulate osteoclast functions.

Original languageEnglish
Pages (from-to)3341-3353
Number of pages13
JournalCellular and Molecular Life Sciences
Volume70
Issue number18
DOIs
Publication statusPublished - 2013 Sep

Keywords

  • Actin ring
  • Circumferential podosome
  • Fusion-competent protrusion
  • IP3
  • PI3-kinase
  • Ruffled border

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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