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From 5F hematopoietic progenitors to osteoclasts: a scalable human model of osteoclastogenesis

IntroductionHuman osteoclast models are essential for studying bone physiology and skeletal disease, yet existing systems are constrained by donor variability and the limited expansion capacity of hematopoietic progenitors.MethodsConditionally expandable 5F hematopoietic stem and progenitor cells ge...

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Autori principali: Malayaperumal, Sarubala (Autore) , Stewart, Sintra (Autore) , Wellington, Rachel (Autore) , Doulatov, Sergei (Autore) , Leber, Elizabeth (Autore) , Scatena, Marta (Autore) , Blümke, Alexander Felix (Autore) , Giachelli, Cecilia M. (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 08 June 2026
In: Frontiers in cell and developmental biology
Year: 2026, Volume: 14, Pages: 1-12
ISSN:2296-634X
DOI:10.3389/fcell.2026.1773507
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fcell.2026.1773507
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1773507/full
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Note sull'autore:Sarubala Malayaperumal, Sintra Stewart, Rachel Wellington, Sergei Doulatov, Elizabeth Leber, Marta Scatena, Alexander Blümke and Cecilia M. Giachelli
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Riassunto:IntroductionHuman osteoclast models are essential for studying bone physiology and skeletal disease, yet existing systems are constrained by donor variability and the limited expansion capacity of hematopoietic progenitors.MethodsConditionally expandable 5F hematopoietic stem and progenitor cells generated by transcription factor reprogramming with HOXA9, ERG, RORA, SOX4, and MYB were differentiated into osteoclasts. Cells were driven through an intermediate monocyte stage using IL three and M CSF, followed by RANKL stimulation to induce osteoclastogenesis.ResultsDifferentiated cells formed large, multinucleated, TRAP positive osteoclasts displaying F actin ring structures, cathepsin K expression, and strong bone resorptive activity. Gene expression analysis demonstrated marked upregulation of key osteoclast markers including NFATC1, MMP9, CTSK, and CA2.DiscussionBy enabling conditional self-renewal at a downstream hematopoietic stage, the 5F platform overcomes key limitations of donor dependent and iPSC derived osteoclast models. This scalable and cytokine driven system provides a reproducible and standardized human osteoclast model suitable for studies of osteoclast biology, bone remodeling, and biomaterial interactions.
Descrizione del documento:Gesehen am 27.07.2026
Descrizione fisica:Online Resource
ISSN:2296-634X
DOI:10.3389/fcell.2026.1773507

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