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YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development
Endochondral ossification requires coordinated mobilization of osteoblast precursors with blood vessels. During adult bone homeostasis, vessel adjacent osteoblast precursors respond to and are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mech...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882292/ https://www.ncbi.nlm.nih.gov/pubmed/36711590 http://dx.doi.org/10.1101/2023.01.20.524918 |
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author | Collins, Joseph M. Lang, Annemarie Parisi, Cristian Moharrer, Yasaman Nijsure, Madhura P. Kim, Jong Hyun (Thomas) Szeto, Greg L. Qin, Ling Gottardi, Riccardo L. Dyment, Nathanial A. Nowlan, Niamh C. Boerckel, Joel D. |
author_facet | Collins, Joseph M. Lang, Annemarie Parisi, Cristian Moharrer, Yasaman Nijsure, Madhura P. Kim, Jong Hyun (Thomas) Szeto, Greg L. Qin, Ling Gottardi, Riccardo L. Dyment, Nathanial A. Nowlan, Niamh C. Boerckel, Joel D. |
author_sort | Collins, Joseph M. |
collection | PubMed |
description | Endochondral ossification requires coordinated mobilization of osteoblast precursors with blood vessels. During adult bone homeostasis, vessel adjacent osteoblast precursors respond to and are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Previously, we found that deletion of the mechanoresponsive transcriptional regulators, YAP and TAZ, from Osterix-expressing osteoblast precursors and their progeny caused perinatal lethality. Here, we show that embryonic YAP/TAZ signaling couples vessel-associated osteoblast precursor mobilization to angiogenesis in developing long bones. Osterix-conditional YAP/TAZ deletion impaired endochondral ossification in the primary ossification center but not intramembranous osteogenesis in the bone collar. Single-cell RNA sequencing revealed YAP/TAZ regulation of the angiogenic chemokine, Cxcl12, which was expressed uniquely in vessel-associated osteoblast precursors. YAP/TAZ signaling spatially coupled osteoblast precursors to blood vessels and regulated vascular morphogenesis and vessel barrier function. Further, YAP/TAZ signaling regulated vascular loop morphogenesis at the chondro-osseous junction to control hypertrophic growth plate remodeling. In human cells, mesenchymal stromal cell co-culture promoted 3D vascular network formation, which was impaired by stromal cell YAP/TAZ depletion, but rescued by recombinant CXCL12 treatment. Lastly, YAP and TAZ mediated mechanotransduction for load-induced osteogenesis in embryonic bone. |
format | Online Article Text |
id | pubmed-9882292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-98822922023-01-28 YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development Collins, Joseph M. Lang, Annemarie Parisi, Cristian Moharrer, Yasaman Nijsure, Madhura P. Kim, Jong Hyun (Thomas) Szeto, Greg L. Qin, Ling Gottardi, Riccardo L. Dyment, Nathanial A. Nowlan, Niamh C. Boerckel, Joel D. bioRxiv Article Endochondral ossification requires coordinated mobilization of osteoblast precursors with blood vessels. During adult bone homeostasis, vessel adjacent osteoblast precursors respond to and are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Previously, we found that deletion of the mechanoresponsive transcriptional regulators, YAP and TAZ, from Osterix-expressing osteoblast precursors and their progeny caused perinatal lethality. Here, we show that embryonic YAP/TAZ signaling couples vessel-associated osteoblast precursor mobilization to angiogenesis in developing long bones. Osterix-conditional YAP/TAZ deletion impaired endochondral ossification in the primary ossification center but not intramembranous osteogenesis in the bone collar. Single-cell RNA sequencing revealed YAP/TAZ regulation of the angiogenic chemokine, Cxcl12, which was expressed uniquely in vessel-associated osteoblast precursors. YAP/TAZ signaling spatially coupled osteoblast precursors to blood vessels and regulated vascular morphogenesis and vessel barrier function. Further, YAP/TAZ signaling regulated vascular loop morphogenesis at the chondro-osseous junction to control hypertrophic growth plate remodeling. In human cells, mesenchymal stromal cell co-culture promoted 3D vascular network formation, which was impaired by stromal cell YAP/TAZ depletion, but rescued by recombinant CXCL12 treatment. Lastly, YAP and TAZ mediated mechanotransduction for load-induced osteogenesis in embryonic bone. Cold Spring Harbor Laboratory 2023-01-21 /pmc/articles/PMC9882292/ /pubmed/36711590 http://dx.doi.org/10.1101/2023.01.20.524918 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Collins, Joseph M. Lang, Annemarie Parisi, Cristian Moharrer, Yasaman Nijsure, Madhura P. Kim, Jong Hyun (Thomas) Szeto, Greg L. Qin, Ling Gottardi, Riccardo L. Dyment, Nathanial A. Nowlan, Niamh C. Boerckel, Joel D. YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development |
title | YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development |
title_full | YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development |
title_fullStr | YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development |
title_full_unstemmed | YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development |
title_short | YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development |
title_sort | yap and taz couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882292/ https://www.ncbi.nlm.nih.gov/pubmed/36711590 http://dx.doi.org/10.1101/2023.01.20.524918 |
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