Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin
BackgroundDisordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine –metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentia...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1234569/full |
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| author | Giusy Di Conza Fulvio Barbaro Nicoletta Zini Nicoletta Zini Giulia Spaletta Giulia Remaggi Lisa Elviri Salvatore Mosca Silvio Caravelli Massimiliano Mosca Roberto Toni Roberto Toni Roberto Toni Roberto Toni |
| author_facet | Giusy Di Conza Fulvio Barbaro Nicoletta Zini Nicoletta Zini Giulia Spaletta Giulia Remaggi Lisa Elviri Salvatore Mosca Silvio Caravelli Massimiliano Mosca Roberto Toni Roberto Toni Roberto Toni Roberto Toni |
| author_sort | Giusy Di Conza |
| collection | DOAJ |
| description | BackgroundDisordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine –metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentiation, woven bone formation, and mineralization by MSCs we looked at the intermediate filament desmin (DES) during the skeletogenic commitment of rat bone marrow MSCs (rBMSCs), where its bone-related action remains elusive.ResultsMonolayer cultures of immunophenotypically- and morphologically - characterized, adult male rBMSCs showed co-localization of desmin (DES) with vimentin, F-actin, and runx2 in all cell morphotypes, each contributing to sparse and dense colonies. Proteomic analysis of these cells revealed a topologically-relevant interactome, focused on cytoskeletal and related enzymes//chaperone/signalling molecules linking DES to runx2 and alkaline phosphatase (ALP). Osteogenic differentiation led to mineralized woven bone nodules confined to dense colonies, significantly smaller and more circular with respect to controls. It significantly increased also colony-forming efficiency and the number of DES-immunoreactive dense colonies, and immunostaining of co-localized DES/runx-2 and DES/ALP. These data confirmed pre-osteoblastic and osteoblastic differentiation, woven bone formation, and mineralization, supporting DES as a player in the molecular pathway leading to the osteogenic fate of rBMSCs.ConclusionImmunocytochemical and morphometric studies coupled with proteomic and bioinformatic analysis support the concept that DES may act as an upstream signal for the skeletogenic commitment of rBMSCs. Thus, we suggest that altered metabolism of osteoblasts, woven bone, and mineralization by dysfunctional BMSCs might early be revealed by changes in DES expression//levels. Non-union fractures and endocrine – metabolic bone disorders like fibrous dysplasia and Paget disease of bone might take advantage of this molecular evidence for their early diagnosis and follow-up. |
| first_indexed | 2024-03-12T02:39:29Z |
| format | Article |
| id | doaj.art-8e8c6d530014497da7c8b89b468d21bd |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-12T02:39:29Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-8e8c6d530014497da7c8b89b468d21bd2023-09-04T09:23:14ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-09-011410.3389/fendo.2023.12345691234569Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desminGiusy Di Conza0Fulvio Barbaro1Nicoletta Zini2Nicoletta Zini3Giulia Spaletta4Giulia Remaggi5Lisa Elviri6Salvatore Mosca7Silvio Caravelli8Massimiliano Mosca9Roberto Toni10Roberto Toni11Roberto Toni12Roberto Toni13Department of Medicine and Surgery - DIMEC, Unit of Biomedical, Biotechnological and Translational Sciences (S.BI.BI.T.), Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S.), and Museum and Historical Library of Biomedicine - BIOMED, University of Parma, Parma, ItalyDepartment of Medicine and Surgery - DIMEC, Unit of Biomedical, Biotechnological and Translational Sciences (S.BI.BI.T.), Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S.), and Museum and Historical Library of Biomedicine - BIOMED, University of Parma, Parma, ItalyUnit of Bologna, National Research Council of Italy (CNR) Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Bologna, ItalyIRCCS Istituto Ortopedico Rizzoli, Bologna, ItalyDepartment of Statistical Sciences, University of Bologna, Bologna, ItalyFood and Drug Department, University of Parma, Parma, ItalyFood and Drug Department, University of Parma, Parma, ItalyCourse on Disorders of the Locomotor System, Fellow Program in Orthopaedics and Traumatology, University Vita-Salute San Raffaele, Milan, ItalyII Clinic of Orthopedic and Traumatology, IRCCS Istituto Ortopedico Rizzoli, Bologna, ItalyII Clinic of Orthopedic and Traumatology, IRCCS Istituto Ortopedico Rizzoli, Bologna, ItalyDepartment of Medicine and Surgery - DIMEC, Unit of Biomedical, Biotechnological and Translational Sciences (S.BI.BI.T.), Laboratory of Regenerative Morphology and Bioartificial Structures (Re.Mo.Bio.S.), and Museum and Historical Library of Biomedicine - BIOMED, University of Parma, Parma, ItalyEndocrinology, Diabetes, and Nutrition Disorders Outpatient Clinic, Osteoporosis, Nutrition, Endocrinology, and Innovative Therapies (OSTEONET) Unit, Galliera Medical Center (GMC), San Venanzio di Galliera, BO, ItalySection IV - Medical Sciences, Academy of Sciences of the Institute of Bologna, Bologna, Italy0Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center - Tufts University School of Medicine, Boston, MA, United StatesBackgroundDisordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine –metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentiation, woven bone formation, and mineralization by MSCs we looked at the intermediate filament desmin (DES) during the skeletogenic commitment of rat bone marrow MSCs (rBMSCs), where its bone-related action remains elusive.ResultsMonolayer cultures of immunophenotypically- and morphologically - characterized, adult male rBMSCs showed co-localization of desmin (DES) with vimentin, F-actin, and runx2 in all cell morphotypes, each contributing to sparse and dense colonies. Proteomic analysis of these cells revealed a topologically-relevant interactome, focused on cytoskeletal and related enzymes//chaperone/signalling molecules linking DES to runx2 and alkaline phosphatase (ALP). Osteogenic differentiation led to mineralized woven bone nodules confined to dense colonies, significantly smaller and more circular with respect to controls. It significantly increased also colony-forming efficiency and the number of DES-immunoreactive dense colonies, and immunostaining of co-localized DES/runx-2 and DES/ALP. These data confirmed pre-osteoblastic and osteoblastic differentiation, woven bone formation, and mineralization, supporting DES as a player in the molecular pathway leading to the osteogenic fate of rBMSCs.ConclusionImmunocytochemical and morphometric studies coupled with proteomic and bioinformatic analysis support the concept that DES may act as an upstream signal for the skeletogenic commitment of rBMSCs. Thus, we suggest that altered metabolism of osteoblasts, woven bone, and mineralization by dysfunctional BMSCs might early be revealed by changes in DES expression//levels. Non-union fractures and endocrine – metabolic bone disorders like fibrous dysplasia and Paget disease of bone might take advantage of this molecular evidence for their early diagnosis and follow-up.https://www.frontiersin.org/articles/10.3389/fendo.2023.1234569/fulldesminintermediate filamentscytoskeletonmesenchymal stromal cellswoven boneosteogenesis |
| spellingShingle | Giusy Di Conza Fulvio Barbaro Nicoletta Zini Nicoletta Zini Giulia Spaletta Giulia Remaggi Lisa Elviri Salvatore Mosca Silvio Caravelli Massimiliano Mosca Roberto Toni Roberto Toni Roberto Toni Roberto Toni Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin Frontiers in Endocrinology desmin intermediate filaments cytoskeleton mesenchymal stromal cells woven bone osteogenesis |
| title | Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin |
| title_full | Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin |
| title_fullStr | Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin |
| title_full_unstemmed | Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin |
| title_short | Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin |
| title_sort | woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin |
| topic | desmin intermediate filaments cytoskeleton mesenchymal stromal cells woven bone osteogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1234569/full |
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