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  Cdc42 in osterix-expressing cells alters osteoblast behavior and myeloid lineage commitment

Wirth, F., Huck, K., Lubosch, A., Zoeller, C., Ghura, H., Porubsky, S., et al. (2021). Cdc42 in osterix-expressing cells alters osteoblast behavior and myeloid lineage commitment. Bone, 153: 116150. doi:10.1016/j.bone.2021.116150.

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 Creators:
Wirth, Franziska1, Author
Huck, Katrin1, Author
Lubosch, Alexander1, Author
Zoeller, Caren1, Author
Ghura, Hiba1, Author
Porubsky, Stefan1, Author
Nakchbandi, Inaam A.2, Author              
Affiliations:
1external, ou_persistent22              
2Nakchbandi, Inaam / Translational Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565162              

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Free keywords: HEMATOPOIETIC STEM-CELLS; RECEPTOR ACTIVATOR; BONE-DEVELOPMENT; STROMAL CELLS; DIFFERENTIATION; SKELETAL; RAC; MYELOPOIESIS; MAINTENANCE; HEDGEHOGEndocrinology & Metabolism; Osteoblast; Hematopoiesis; Myelopoiesis; Rho GTPase; Cdc42; Osteoblast differentiation; Bone formation; Mesenchymal stromal cell; Bone marrow niche; Hematopoietic niche; Interleukin-4; Osterix; Collagen 2.3-Cre;
 Abstract: Osteoblasts are not only responsible for bone formation. They also support hematopoiesis. This requires responding to cues originating from several signaling pathways, a task performed by Rho GTPases. We therefore examined several transgenic mouse models and used inhibitors of Cdc42 in vitro. Deletion of Cdc42 in vivo using the Osterix promoter suppressed osteoblast function, while its deletion in differentiating osteoblasts using the Collagen-a1(I) promoter decreased osteoblast numbers. In both cases, bone mineral density diminished confirming the importance of Cdc42. Evaluation of hematopoiesis revealed that deletion of Cdc42 using the Osterix, but not the Collagen-a1(I) promoter increased the common myeloid progenitors (CMPs) in the bone marrow as well as the erythrocytes and the thrombocytes/platelets in peripheral blood. Causality between Cdc42 loss in early osteoblasts and increased myelopoiesis was confirmed in vitro. Work in vitro supported the conclusion that interleukin-4 mediated the increase in myelopoiesis. Thus, Cdc42 is required for healthy bone through regulation of bone formation in Osterix-expressing osteoblasts and the number of osteoblasts in differentiating osteoblasts. In addition, its expression in early osteoblasts/ stromal cells modulates myelopoiesis. This highlights the importance of osteoblasts in regulating hematopoiesis.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Bone
  Other : Bone
Source Genre: Journal
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Publ. Info: New York : Elsevier
Pages: - Volume / Issue: 153 Sequence Number: 116150 Start / End Page: - Identifier: ISSN: 8756-3282
CoNE: https://pure.mpg.de/cone/journals/resource/954927629281