Abstract

Osteoclasts form a specialized cell–matrix adhesion structure, known as the “sealing zone”, during bone resorption. The sealing zone is a dynamic actin-rich structure that defines the resorption area of the bone. The detailed dynamics and fine structure of the sealing zone have been elusive. Osteoclasts plated on glass do not form a sealing zone, but generate a separate supra-molecular structure called the “podosome belt”. Podosomes are integrin-based adhesion complexes involved in matrix adhesion, cell migration, matrix degradation, and mechanosensing. Invadopodia, podosome-like protrusions in cancer cells, are involved in cell invasion into other tissues by promoting matrix degradation. Both podosomes and invadopodia exhibit actin pattern transitions during maturation. We previously found that Arp2/3-dependent actin flow occurs in all observed assembly patterns of podosomes in osteoclasts on glass. It is known that the actin wave in Dictyostelium cells exhibits a similar pattern transition in its evolution. Because of significant advances in our understanding regarding the mechanism of podosomes/invadopodia formation over the last decade, we revisited the structure and function of the sealing zone in this review, highlighting the possible involvement of self-organized actin waves in the organogenesis of the sealing zone.

Highlights

  • Osteoclasts are giant multinucleated cells responsible for bone resorption

  • Because we have already reviewed the role of actin flow in the podosome field elsewhere [7], the present study concentrates on the role of actin waves in the organogenesis of the sealing zone

  • Plasticity and dynamics are vital for the function of the sealing zone, because osteoclasts attach on the rugged surface of the bone and segregate the area of bone resorption via the sealing zone

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Summary

Introduction

They form the sealing zone, a bone-anchored adhesion structure between the bone and the osteoclasts. The podosome is an actin-rich matrix-anchored complex found in various cells, including macrophages, dendritic cells, and osteoclasts [1,2]. We recently found that retrograde actin flow occurs in a podosome-derived structure within osteoclasts [6]. This information has shed light on the nature of the sealing zone of osteoclasts. The unique actin-rich adhesive structures in normal cells have been called podosomes, whereas in cancer cells, they are known as invadopodia. In this review, we follow the traditional naming to clearly distinguish between the specific structure and function within a given cell

Bone Resorption by Osteoclasts
Podosomes and the Sealing Zone
The Sealing Zone on Bone Is Different from the Podosome Belt on Glass
Size of the Sealing Zone
Discovery of Self-Organized Actin Flow in Osteoclasts
Actin Waves in Dictyostelium Cells and Actin Flow in Osteoclasts
The Behavior of the Actin Wavse in a Large Space
Organization of the Podosome Field
Two Substructures of the Podosome Belt
Formation of Actin Core with the Adhesion Domain
Formation of the Actin Flow
Diffusion Barrier
Matrix Degradation
Findings
Perspectives
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