Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin

Frontiers in Endocrinology

Endocrinology

Salvatore Mosca¹  Giusy Di Conza²  Fulvio Barbaro²  Roberto Toni³  Giulia Spaletta⁴  Giulia Remaggi⁵  Lisa Elviri⁵  Massimiliano Mosca⁶  Silvio Caravelli⁶  Nicoletta Zini⁷ 

[1] Course on Disorders of the Locomotor System, Fellow Program in Orthopaedics and Traumatology, University Vita-Salute San Raffaele, Milan, Italy;Department 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, Italy;Department 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, Italy;Endocrinology, Diabetes, and Nutrition Disorders Outpatient Clinic, Osteoporosis, Nutrition, Endocrinology, and Innovative Therapies (OSTEONET) Unit, Galliera Medical Center (GMC), San Venanzio di Galliera, BO, Italy;Section IV - Medical Sciences, Academy of Sciences of the Institute of Bologna, Bologna, Italy;Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center - Tufts University School of Medicine, Boston, MA, United States;Department of Statistical Sciences, University of Bologna, Bologna, Italy;Food and Drug Department, University of Parma, Parma, Italy;II Clinic of Orthopedic and Traumatology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy;Unit of Bologna, National Research Council of Italy (CNR) Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Bologna, Italy;IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy;

关键词: desmin;    intermediate filaments;    cytoskeleton;    mesenchymal stromal cells;    woven bone;    osteogenesis;    non-union fractures;    metabolic skeletal dysplasia;   

DOI  :  10.3389/fendo.2023.1234569

 received in 2023-06-04, accepted in 2023-08-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Di Conza, Barbaro, Zini, Spaletta, Remaggi, Elviri, Mosca, Caravelli, Mosca and Toni