Podosome organization drives osteoclast-mediated bone resorption.
Osteoclasts are the cells responsible for physiological bone resorption. A specific organization of their most prominent cytoskeletal structures, podosomes, is crucial for the degradation of mineralized bone matrix. Each podosome is constituted of an F-actin-enriched central core surrounded by a loose F-actin network, called the podosome cloud. In addition to intrinsic actin dynamics, podosomes are defined by their adhesion to the extracellular matrix, mainly via core-linking CD44 and cloud-linking integrins. These properties allow podosomes to collectively evolve into different patterns implicated in migration and bone resorption. Indeed, to resorb bone, osteoclasts polarize, actively secrete protons, and proteases into the resorption pit where these molecules are confined by a podosome-containing sealing zone. Here, we review recent advancements on podosome structure and regulatory pathways in osteoclasts. We also discuss the distinct functions of different podosome patterns during the lifespan of a single osteoclast.
Institut de Génomique Fonctionnelle de Lyon; Université de Lyon; Ecole Normale Supérieure de Lyon; Lyon, France.
Dan
D
Georgess
Institut de Génomique Fonctionnelle de Lyon; Université de Lyon; Ecole Normale Supérieure de Lyon; Lyon, France.
Irma
I
Machuca-Gayet
Centre de Recherche de Biochimie Macromoléculaire; CNRS UMR 5237; Montpellier University; Montpellier, France.
Anne
A
Blangy
Institut de Génomique Fonctionnelle de Lyon; Université de Lyon; Ecole Normale Supérieure de Lyon; Lyon, France.
Pierre
P
Jurdic
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*
actin; actin rings; bone degradation; migration; osteoclasts; podosomes; sealing zone