scholarly journals Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts

2014 ◽  
Vol 25 (3) ◽  
pp. 380-396 ◽  
Author(s):  
Dan Georgess ◽  
Marlène Mazzorana ◽  
José Terrado ◽  
Christine Delprat ◽  
Christophe Chamot ◽  
...  

The function of osteoclasts (OCs), multinucleated giant cells (MGCs) of the monocytic lineage, is bone resorption. To resorb bone, OCs form podosomes. These are actin-rich adhesive structures that pattern into rings that drive OC migration and into “sealing-zones” (SZs) that confine the resorption lacuna. Although changes in actin dynamics during podosome patterning have been documented, the mechanisms that regulate these changes are largely unknown. From human monocytic precursors, we differentiated MGCs that express OC degradation enzymes but are unable to resorb the mineral matrix. We demonstrated that, despite exhibiting bona fide podosomes, these cells presented dysfunctional SZs. We then performed two-step differential transcriptomic profiling of bone-resorbing OCs versus nonresorbing MGCs to generate a list of genes implicated in bone resorption. From this list of candidate genes, we investigated the role of Rho/Rnd3. Using primary RhoE-deficient OCs, we demonstrated that RhoE is indispensable for OC migration and bone resorption by maintaining fast actin turnover in podosomes. We further showed that RhoE activates podosome component cofilin by inhibiting its Rock-mediated phosphorylation. We conclude that the RhoE-Rock-cofilin pathway, by promoting podosome dynamics and patterning, is central for OC migration, SZ formation, and, ultimately, bone resorption.

2019 ◽  
Vol 108 (1) ◽  
pp. 282-297 ◽  
Author(s):  
Ana Carolina Cestari Bighetti ◽  
Tania Mary Cestari ◽  
Paula Sanches Santos ◽  
Ricardo Vinicius Nunes Arantes ◽  
Suelen Paini ◽  
...  

1999 ◽  
Vol 30 (11) ◽  
pp. 1383-1388 ◽  
Author(s):  
Silloo B Kapadia ◽  
Clayton A Wiley ◽  
Virawudh Soontornniyomkij ◽  
Guoji Wang ◽  
Steven H Swerdlow

2004 ◽  
Vol 15 (12) ◽  
pp. 5231-5241 ◽  
Author(s):  
Frédéric Saltel ◽  
Olivier Destaing ◽  
Frédéric Bard ◽  
Diane Eichert ◽  
Pierre Jurdic

The actin cytoskeleton is essential for osteoclasts main function, bone resorption. Two different organizations of actin have been described in osteoclasts, the podosomes belt corresponding to numerous F-actin columns arranged at the cell periphery, and the sealing zone defined as a unique large band of actin. To compare the role of these two different actin organizations, we imaged osteoclasts on various substrata: glass, dentin, and apatite. Using primary osteoclasts expressing GFP-actin, we found that podosome belts and sealing zones, both very dynamic actin structures, were present in mature osteoclasts; podosome belts were observed only in spread osteoclasts adhering onto glass, whereas sealing zone were seen in apico-basal polarized osteoclasts adherent on mineralized matrix. Dynamic observations of several resorption cycles of osteoclasts seeded on apatite revealed that 1) podosomes do not fuse together to form the sealing zone; 2) osteoclasts alternate successive stationary polarized resorption phases with a sealing zone and migration, nonresorption phases without any specific actin structure; and 3) apatite itself promotes sealing zone formation though c-src and Rho signaling. Finally, our work suggests that apatite-mediated sealing zone formation is dependent on both c-src and Rho whereas apico-basal polarization requires only Rho.


BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antoni Olona ◽  
Subhankar Mukhopadhyay ◽  
Charlotte Hateley ◽  
Fernando O. Martinez ◽  
Siamon Gordon ◽  
...  

AbstractCell membrane fusion and multinucleation in macrophages are associated with physiologic homeostasis as well as disease. Osteoclasts are multinucleated macrophages that resorb bone through increased metabolic activity resulting from cell fusion. Fusion of macrophages also generates multinucleated giant cells (MGCs) in white adipose tissue (WAT) of obese individuals. For years, our knowledge of MGCs in WAT has been limited to their description as part of crown-like structures (CLS) surrounding damaged adipocytes. However, recent evidence indicates that these cells can phagocytose oversized lipid remnants, suggesting that, as in osteoclasts, cell fusion and multinucleation are required for specialized catabolic functions. We thus reason that WAT MGCs can be viewed as functionally analogous to osteoclasts and refer to them in this article as adipoclasts. We first review current knowledge on adipoclasts and their described functions. In view of recent advances in single cell genomics, we describe WAT macrophages from a ‘fusion perspective’ and speculate on the ontogeny of adipoclasts. Specifically, we highlight the role of CD9 and TREM2, two plasma membrane markers of lipid-associated macrophages in WAT, which have been previously described as regulators of fusion and multinucleation in osteoclasts and MGCs. Finally, we consider whether strategies aiming to target WAT macrophages can be more selectively directed against adipoclasts.


2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Seema Lale ◽  
Daniel Soto ◽  
Patricia G. Wasserman

Langerhan’s cell histiocytosis (LCH) results from the proliferation of immunophenotypically and functionally immature, morphologically rounded Langerhan’s cells along with eosinophils, macrophages, lymphocytes, and, commonly, multinucleated giant cells. Here we report a case in a 6-year-old boy of differential diagnoses including dermatopathic lymphadenitis (DL), parasitic infection, Kimura’s disease, hypersensitivity reactions, cat-scratch disease, sinus histiocytosis with massive lymphadenopathy (SHML), hyperplasic lymph nodes, and lymphoma.


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