Basics on bone cells: osteoclasts
ECTS eCampus. Sobacchi C. 07/04/22; 369946
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Bone is reshaped and renewed throughout life by the processes of bone modeling and remodeling, respectively, which depend on the coordinated action of osteoblasts, osteoclasts, and osteocytes. In particular, osteoclasts are large, multi-nucleated phagocytic cells of hematopoietic origin, generated through fusion of embryonic erythro-myeloid progenitors during fetal life, and maintained in postnatal life by fusion of Hematopoietic Stem Cell (HSC)-derived monocytic precursors.1 Cell fate specification in response to stimulation with the essential osteoclastogenic factors M-CSF and RANKL, occurs through a molecularly-defined stepwise fate decision pathway, recently investigated at the single cell level.2 Osteoclasts are the exclusive bone-resorbing cells; this activity requires a complex resorption machinery made of specialized membrane regions, vesicles and molecules,3 and can be carried out in two modes, a stationary and a migratory one, giving rise respectively to pits and trenches.4 Moreover, mature osteoclasts can undergo fission in vivo, generating smaller multi-nucleated “osteomorphs” that can re-enter the fusion process and contribute again to the formation of mature osteoclasts.5 This basic knowledge of osteoclast biology has translational relevance in human bone pathophysiology.
1. Jacome-Galarza CE, et al. Developmental origin, functional maintenance and genetic rescue of osteoclasts. Nature. 2019 Apr;568(7753):541-545. doi: 10.1038/s41586-019-1105-7.
2. Tsukasaki M, et al. Stepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution. Nat Metab. 2020 Dec;2(12):1382-1390. doi: 10.1038/s42255-020-00318-y.
3. Elson A, et al. Sorting Nexin 10 as a Key Regulator of Membrane Trafficking in Bone-Resorbing Osteoclasts: Lessons Learned From Osteopetrosis. Front Cell Dev Biol. 2021 May 20;9:671210. doi: 10.3389/fcell.2021.671210.
4. Delaisse JM, et al. The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption. Front Cell Dev Biol. 2021 Mar 30;9:644503. doi: 10.3389/fcell.2021.644503.
5. McDonald MM, et al. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption. Cell. 2021 Apr 1;184(7):1940. doi: 10.1016/j.cell.2021.03.010
2. Tsukasaki M, et al. Stepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution. Nat Metab. 2020 Dec;2(12):1382-1390. doi: 10.1038/s42255-020-00318-y.
3. Elson A, et al. Sorting Nexin 10 as a Key Regulator of Membrane Trafficking in Bone-Resorbing Osteoclasts: Lessons Learned From Osteopetrosis. Front Cell Dev Biol. 2021 May 20;9:671210. doi: 10.3389/fcell.2021.671210.
4. Delaisse JM, et al. The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption. Front Cell Dev Biol. 2021 Mar 30;9:644503. doi: 10.3389/fcell.2021.644503.
5. McDonald MM, et al. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption. Cell. 2021 Apr 1;184(7):1940. doi: 10.1016/j.cell.2021.03.010
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