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Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation

Matrix metalloproteases (MMPs) play crucial roles in extracellular matrix (ECM) modulation during osteoclast-driven bone remodeling. In the present study, we used transcriptome profiling of bone cells in a medaka model for osteoporosis and bone regeneration to identify factors critical for bone remo...

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Autores principales: Liu, Ranran, Imangali, Nurgul, Ethiraj, Lalith Prabha, Carney, Tom James, Winkler, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911226/
https://www.ncbi.nlm.nih.gov/pubmed/35281094
http://dx.doi.org/10.3389/fcell.2022.775512
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author Liu, Ranran
Imangali, Nurgul
Ethiraj, Lalith Prabha
Carney, Tom James
Winkler, Christoph
author_facet Liu, Ranran
Imangali, Nurgul
Ethiraj, Lalith Prabha
Carney, Tom James
Winkler, Christoph
author_sort Liu, Ranran
collection PubMed
description Matrix metalloproteases (MMPs) play crucial roles in extracellular matrix (ECM) modulation during osteoclast-driven bone remodeling. In the present study, we used transcriptome profiling of bone cells in a medaka model for osteoporosis and bone regeneration to identify factors critical for bone remodeling and homeostasis. This identified mmp13b, which was strongly expressed in osteoblast progenitors and upregulated under osteoporotic conditions and during regeneration of bony fin rays. To characterize the role of mmp13b in bone remodeling, we generated medaka mmp13b mutants by CRISPR/Cas9. We found that mmp13b mutants form normal numbers of osteoblasts and osteoclasts. However, osteoclast activity was severely impaired under osteoporotic conditions. In mmp13b mutants and embryos treated with the MMP13 inhibitor CL-82198, unmineralized collagens and mineralized bone matrix failed to be degraded. In addition, the dynamic migratory behavior of activated osteoclasts was severely affected in mmp13b mutants. Expression analysis showed that maturation genes were downregulated in mmp13b deficient osteoclasts suggesting that they remain in an immature and non-activated state. We also found that fin regeneration was delayed in mmp13b mutants with a concomitant alteration of the ECM and reduced numbers of osteoblast progenitors in regenerating joint regions. Together, our findings suggest that osteoblast-derived Mmp13b alters the bone ECM to allow the maturation and activation of osteoclasts during bone remodeling in a paracrine manner. Mmp13b-induced ECM alterations are also required to facilitate osteoblast progenitor recruitment and full regeneration of bony fin rays.
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spelling pubmed-89112262022-03-11 Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation Liu, Ranran Imangali, Nurgul Ethiraj, Lalith Prabha Carney, Tom James Winkler, Christoph Front Cell Dev Biol Cell and Developmental Biology Matrix metalloproteases (MMPs) play crucial roles in extracellular matrix (ECM) modulation during osteoclast-driven bone remodeling. In the present study, we used transcriptome profiling of bone cells in a medaka model for osteoporosis and bone regeneration to identify factors critical for bone remodeling and homeostasis. This identified mmp13b, which was strongly expressed in osteoblast progenitors and upregulated under osteoporotic conditions and during regeneration of bony fin rays. To characterize the role of mmp13b in bone remodeling, we generated medaka mmp13b mutants by CRISPR/Cas9. We found that mmp13b mutants form normal numbers of osteoblasts and osteoclasts. However, osteoclast activity was severely impaired under osteoporotic conditions. In mmp13b mutants and embryos treated with the MMP13 inhibitor CL-82198, unmineralized collagens and mineralized bone matrix failed to be degraded. In addition, the dynamic migratory behavior of activated osteoclasts was severely affected in mmp13b mutants. Expression analysis showed that maturation genes were downregulated in mmp13b deficient osteoclasts suggesting that they remain in an immature and non-activated state. We also found that fin regeneration was delayed in mmp13b mutants with a concomitant alteration of the ECM and reduced numbers of osteoblast progenitors in regenerating joint regions. Together, our findings suggest that osteoblast-derived Mmp13b alters the bone ECM to allow the maturation and activation of osteoclasts during bone remodeling in a paracrine manner. Mmp13b-induced ECM alterations are also required to facilitate osteoblast progenitor recruitment and full regeneration of bony fin rays. Frontiers Media S.A. 2022-02-21 /pmc/articles/PMC8911226/ /pubmed/35281094 http://dx.doi.org/10.3389/fcell.2022.775512 Text en Copyright © 2022 Liu, Imangali, Ethiraj, Carney and Winkler. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Liu, Ranran
Imangali, Nurgul
Ethiraj, Lalith Prabha
Carney, Tom James
Winkler, Christoph
Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation
title Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation
title_full Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation
title_fullStr Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation
title_full_unstemmed Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation
title_short Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation
title_sort transcriptome profiling of osteoblasts in a medaka (oryzias latipes) osteoporosis model identifies mmp13b as crucial for osteoclast activation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911226/
https://www.ncbi.nlm.nih.gov/pubmed/35281094
http://dx.doi.org/10.3389/fcell.2022.775512
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