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Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma

Multiple myeloma is characterized by bone lesions linked to increased osteoclast and decreased osteoblast activities. In particular, the osteoblast differentiation of bone marrow-derived stem cells (MSC) is impaired. Among the potential therapeutic tools for counteracting bone lesions, adipose-deriv...

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Autores principales: Béréziat, Véronique, Mazurier, Christelle, Auclair, Martine, Ferrand, Nathalie, Jolly, Séverine, Marie, Tiffany, Kobari, Ladan, Toillon, Indira, Delhommeau, François, Fève, Bruno, Larsen, Annette K., Sabbah, Michèle, Garderet, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562713/
https://www.ncbi.nlm.nih.gov/pubmed/31083455
http://dx.doi.org/10.3390/cells8050441
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author Béréziat, Véronique
Mazurier, Christelle
Auclair, Martine
Ferrand, Nathalie
Jolly, Séverine
Marie, Tiffany
Kobari, Ladan
Toillon, Indira
Delhommeau, François
Fève, Bruno
Larsen, Annette K.
Sabbah, Michèle
Garderet, Laurent
author_facet Béréziat, Véronique
Mazurier, Christelle
Auclair, Martine
Ferrand, Nathalie
Jolly, Séverine
Marie, Tiffany
Kobari, Ladan
Toillon, Indira
Delhommeau, François
Fève, Bruno
Larsen, Annette K.
Sabbah, Michèle
Garderet, Laurent
author_sort Béréziat, Véronique
collection PubMed
description Multiple myeloma is characterized by bone lesions linked to increased osteoclast and decreased osteoblast activities. In particular, the osteoblast differentiation of bone marrow-derived stem cells (MSC) is impaired. Among the potential therapeutic tools for counteracting bone lesions, adipose-derived stem cells (ASC) could represent an appealing source for regenerative medicine due to their similar characteristics with MSC. Our study is among the first giving detailed insights into the osteoblastogenic capacities of ASC isolated by fat aspiration from myeloma patients (MM-ASC) compared to healthy subjects (HD-ASC). We showed that MM-ASC and HD-ASC exhibited comparable morphology, proliferative capacity, and immunophenotype. Unexpectedly, although normal in adipocyte differentiation, MM-ASC present a defective osteoblast differentiation, as indicated by less calcium deposition, decreased alkaline phosphatase activity, and downregulation of RUNX2 and osteocalcin. Furthermore, these ASC-derived osteoblasts displayed enhanced senescence, as shown by an increased β-galactosidase activity and cell cycle inhibitors expression (p16(INK4A), p21(WAF1/CIP1).), associated with a markedly increased expression of DKK1, a major inhibitor of osteoblastogenesis in multiple myeloma. Interestingly, inhibition of DKK1 attenuated senescence and rescued osteoblast differentiation, highlighting its key role. Our findings show, for the first time, that multiple myeloma is a systemic disease and suggest that ASC from patients would be unsuitable for tissue engineering designed to treat myeloma-associated bone disease.
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spelling pubmed-65627132019-06-17 Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma Béréziat, Véronique Mazurier, Christelle Auclair, Martine Ferrand, Nathalie Jolly, Séverine Marie, Tiffany Kobari, Ladan Toillon, Indira Delhommeau, François Fève, Bruno Larsen, Annette K. Sabbah, Michèle Garderet, Laurent Cells Article Multiple myeloma is characterized by bone lesions linked to increased osteoclast and decreased osteoblast activities. In particular, the osteoblast differentiation of bone marrow-derived stem cells (MSC) is impaired. Among the potential therapeutic tools for counteracting bone lesions, adipose-derived stem cells (ASC) could represent an appealing source for regenerative medicine due to their similar characteristics with MSC. Our study is among the first giving detailed insights into the osteoblastogenic capacities of ASC isolated by fat aspiration from myeloma patients (MM-ASC) compared to healthy subjects (HD-ASC). We showed that MM-ASC and HD-ASC exhibited comparable morphology, proliferative capacity, and immunophenotype. Unexpectedly, although normal in adipocyte differentiation, MM-ASC present a defective osteoblast differentiation, as indicated by less calcium deposition, decreased alkaline phosphatase activity, and downregulation of RUNX2 and osteocalcin. Furthermore, these ASC-derived osteoblasts displayed enhanced senescence, as shown by an increased β-galactosidase activity and cell cycle inhibitors expression (p16(INK4A), p21(WAF1/CIP1).), associated with a markedly increased expression of DKK1, a major inhibitor of osteoblastogenesis in multiple myeloma. Interestingly, inhibition of DKK1 attenuated senescence and rescued osteoblast differentiation, highlighting its key role. Our findings show, for the first time, that multiple myeloma is a systemic disease and suggest that ASC from patients would be unsuitable for tissue engineering designed to treat myeloma-associated bone disease. MDPI 2019-05-10 /pmc/articles/PMC6562713/ /pubmed/31083455 http://dx.doi.org/10.3390/cells8050441 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Béréziat, Véronique
Mazurier, Christelle
Auclair, Martine
Ferrand, Nathalie
Jolly, Séverine
Marie, Tiffany
Kobari, Ladan
Toillon, Indira
Delhommeau, François
Fève, Bruno
Larsen, Annette K.
Sabbah, Michèle
Garderet, Laurent
Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma
title Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma
title_full Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma
title_fullStr Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma
title_full_unstemmed Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma
title_short Systemic Dysfunction of Osteoblast Differentiation in Adipose-Derived Stem Cells from Patients with Multiple Myeloma
title_sort systemic dysfunction of osteoblast differentiation in adipose-derived stem cells from patients with multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562713/
https://www.ncbi.nlm.nih.gov/pubmed/31083455
http://dx.doi.org/10.3390/cells8050441
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