{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:27:15Z","timestamp":1792016835640,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAR 2019 Interdepartmental Grant, awarded by the University of Modena and Reggio Emilia"},{"name":"MIUR-PRIN 2017_RKWNJT"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1\/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk.<\/jats:p>","DOI":"10.3390\/biom14101243","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T03:57:52Z","timestamp":1727755072000},"page":"1243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Myoblast-Derived Galectin 3 Impairs the Early Phases of Osteogenesis Affecting Notch and Akt Activity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6348-4960","authenticated-orcid":false,"given":"Emanuela","family":"Amore","sequence":"first","affiliation":[{"name":"Laboratorio Ramses, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-1840","authenticated-orcid":false,"given":"Vittoria","family":"Cenni","sequence":"additional","affiliation":[{"name":"CNR-Institute of Molecular Genetics, 40136 Bologna, Italy"},{"name":"IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-2757","authenticated-orcid":false,"given":"Manuela","family":"Piazzi","sequence":"additional","affiliation":[{"name":"CNR-Institute of Molecular Genetics, 40136 Bologna, Italy"},{"name":"IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0262-842X","authenticated-orcid":false,"given":"Michele","family":"Signore","sequence":"additional","affiliation":[{"name":"RPPA Unit of Proteomics Area, Core Facilities, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3257-6293","authenticated-orcid":false,"given":"Simona","family":"Neri","sequence":"additional","affiliation":[{"name":"Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8631-3419","authenticated-orcid":false,"given":"Stefano","family":"Biressi","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-3640","authenticated-orcid":false,"given":"Rosario","family":"Barone","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-1260","authenticated-orcid":false,"given":"Valentina","family":"Di Felice","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde Y.","family":"Follo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40127 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessika","family":"Bertacchini","sequence":"additional","affiliation":[{"name":"CNR-Institute of Molecular Genetics, 40136 Bologna, Italy"},{"name":"Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0587-0112","authenticated-orcid":false,"given":"Carla","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1440-2440(00)80040-7","article-title":"Functional adaptation of bone to exercise and injury","volume":"3","author":"Wohl","year":"2000","journal-title":"J. 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