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

Frontiers in Endocrinology · 10 authors, 10 centres

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An in vitro study of rat bone marrow mesenchymal stromal cells (rBMSCs) found that the cytoskeletal protein desmin (DES) co-localizes with key osteogenic factors and its expression increases during osteogenic differentiation, suggesting it may act as an upstream signal for bone formation and mineralization.

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This preclinical in vitro study used immunophenotypically characterized adult male rat bone marrow mesenchymal stromal cells (rBMSCs) to investigate the role of the intermediate filament desmin (DES) in osteogenic differentiation. Cells were cultured on rigid substrates to favor skeletogenic commitment. Results showed that DES co-localized with vimentin, F-actin, and runx2 across cell morphotypes. Proteomic analysis revealed an interactome linking DES to runx2 and alkaline phosphatase (ALP). Osteogenic induction led to significantly smaller, more circular mineralized woven bone nodules and significantly increased colony-forming efficiency, DES-immunoreactive dense colonies, and immunostaining for DES/runx-2 and DES/ALP, confirming differentiation. The study concludes DES may be an upstream signal in the molecular pathway for rBMSC skeletogenic commitment.

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preclinical research

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ORIGINAL PAPER

PMC10507407

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

Frontiers in Endocrinology

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ABSTRACT

Background Disordered 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. Results Monolayer 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. Conclusion Immunocytochemical 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.

CITATION EXPORT

Giusy Di Conza, Fulvio Barbaro, Nicoletta Zini et al.. Woven bone formation and mineralization by rat mesenchymal stromal cells imply increased expression of the intermediate filament desmin. Frontiers in Endocrinology. (2023). https://doi.org/10.3389/fendo.2023.1234569

AUTHORS

10 · 10 CENTRES

Giusy Di Conza, Fulvio Barbaro, Nicoletta Zini, Giulia Spaletta, Giulia Remaggi, Lisa Elviri, Salvatore Mosca, Silvio Caravelli, Massimiliano Mosca, Roberto Toni

1Department 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
2Unit of Bologna, National Research Council of Italy (CNR) Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Bologna, Italy
3IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
4Department of Statistical Sciences, University of Bologna, Bologna, Italy
5Food and Drug Department, University of Parma, Parma, Italy
6Course on Disorders of the Locomotor System, Fellow Program in Orthopaedics and Traumatology, University Vita-Salute San Raffaele, Milan, Italy
7II Clinic of Orthopedic and Traumatology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
8Endocrinology, Diabetes, and Nutrition Disorders Outpatient Clinic, Osteoporosis, Nutrition, Endocrinology, and Innovative Therapies (OSTEONET) Unit, Galliera Medical Center (GMC), San Venanzio di Galliera, BO, Italy
9Section IV - Medical Sciences, Academy of Sciences of the Institute of Bologna, Bologna, Italy
10Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center - Tufts University School of Medicine, Boston, MA, United States