Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis
Abstract Background Osteoporosis (OP), characterized by reduced bone mass and mineral density, is a global metabolic disorder that severely impacts the quality of life in affected individuals. Although current pharmacological treatments are effective, their long-term use is often associated with adv...
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2025-02-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04165-0 |
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| author | Alberto González-González Itziar Álvarez-Iglesias Daniel García-Sánchez Monica Dotta Ricardo Reyes Ana Alfonso-Fernández Alfonso Bolado-Carrancio Patricia Díaz-Rodríguez María Isabel Pérez-Núñez José Carlos Rodríguez-Rey Jesús Delgado-Calle Flor M. Pérez-Campo |
| author_facet | Alberto González-González Itziar Álvarez-Iglesias Daniel García-Sánchez Monica Dotta Ricardo Reyes Ana Alfonso-Fernández Alfonso Bolado-Carrancio Patricia Díaz-Rodríguez María Isabel Pérez-Núñez José Carlos Rodríguez-Rey Jesús Delgado-Calle Flor M. Pérez-Campo |
| author_sort | Alberto González-González |
| collection | DOAJ |
| description | Abstract Background Osteoporosis (OP), characterized by reduced bone mass and mineral density, is a global metabolic disorder that severely impacts the quality of life in affected individuals. Although current pharmacological treatments are effective, their long-term use is often associated with adverse effects, highlighting the need for safer, more sustainable therapeutic strategies. This study investigates the pro-osteogenic and anti-resorptive potential of the secretome from Smurf1-silenced mesenchymal stem cells (MSCs) as a promising cell-free therapy for bone regeneration. Methods Conditioned media (CM) from Smurf1-silenced rat (rCM-Smur1) and human MSCs (hCM-Smurf1) was collected and analyzed. Pro-osteogenic potential was assessed by measuring in vitro mineralization in human and rat MSCs cultures. In vivo, studies were conducted using a rat ectopic bone formation model and a post-menopausal osteoporotic mouse model. Additionally, primary human osteoporotic MSCs were preconditioned with hCM-Smurf1, and their osteogenic capacity was compared to that induced by BMP2 treatment. Ex vivo, human bone explants were treated with hCM-Smurf1 to assess anti-resorptive effects. Proteomic analysis of the soluble and vesicular CM fractions identified key proteins involved in bone regeneration. Results CM from Smurf1-silenced MSCs significantly enhanced mineralization in vitro and bone formation in vivo. Preconditioning human osteoporotic MSCs with hCM-Smurf1 significantly increases in vitro mineralization, with levels comparable to those achieved with BMP2 treatment. Additionally, in ex vivo human bone cultures, treatment with hCM-Smurf1 significantly reduced RANKL expression without affecting OPG levels, indicating an anti-resorptive effect. In vivo, CM from Smurf1-silenced MSCs significantly increased bone formation in a rat ectopic model, and its local administration reduced trabecular bone loss by 50% in a post-menopausal osteoporotic mouse model after a single administration within just four weeks. Proteomic analysis revealed both soluble and vesicular fractions of hCM-Smurf1 were enriched with proteins essential for ossification and extracellular matrix organization, enhancing osteogenic differentiation. Conclusions The Smurf1-silenced MSCs' secretome shows potent osteogenic and anti-resorptive effects, significantly enhancing bone formation and reducing bone loss. This study provides compelling evidence for the therapeutic potential of Smurf1-silenced MSC-derived secretome as a non-toxic and targeted treatment for osteoporosis. These findings warrant further in vivo studies and clinical trials to validate its therapeutic efficacy and safety. |
| format | Article |
| id | doaj-art-050a77158cbe4a59a8c11f5b6715935e |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj-art-050a77158cbe4a59a8c11f5b6715935e2025-02-09T12:15:45ZengBMCStem Cell Research & Therapy1757-65122025-02-0116112010.1186/s13287-025-04165-0Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosisAlberto González-González0Itziar Álvarez-Iglesias1Daniel García-Sánchez2Monica Dotta3Ricardo Reyes4Ana Alfonso-Fernández5Alfonso Bolado-Carrancio6Patricia Díaz-Rodríguez7María Isabel Pérez-Núñez8José Carlos Rodríguez-Rey9Jesús Delgado-Calle10Flor M. Pérez-Campo11Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALDepartment of Physiology and Cell Biology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical SciencesDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALDepartment of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La LagunaDepartment of Traumatology, Hospital Universitario Marqués de Valdecilla, University of CantabriaCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of EdinburghI+D Farma Group (GI-1645), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Facultad de Farmacia, Instituto de Materiales (iMATUS) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de CompostelaDepartment of Traumatology, Hospital Universitario Marqués de Valdecilla, University of CantabriaDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALDepartment of Physiology and Cell Biology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical SciencesDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALAbstract Background Osteoporosis (OP), characterized by reduced bone mass and mineral density, is a global metabolic disorder that severely impacts the quality of life in affected individuals. Although current pharmacological treatments are effective, their long-term use is often associated with adverse effects, highlighting the need for safer, more sustainable therapeutic strategies. This study investigates the pro-osteogenic and anti-resorptive potential of the secretome from Smurf1-silenced mesenchymal stem cells (MSCs) as a promising cell-free therapy for bone regeneration. Methods Conditioned media (CM) from Smurf1-silenced rat (rCM-Smur1) and human MSCs (hCM-Smurf1) was collected and analyzed. Pro-osteogenic potential was assessed by measuring in vitro mineralization in human and rat MSCs cultures. In vivo, studies were conducted using a rat ectopic bone formation model and a post-menopausal osteoporotic mouse model. Additionally, primary human osteoporotic MSCs were preconditioned with hCM-Smurf1, and their osteogenic capacity was compared to that induced by BMP2 treatment. Ex vivo, human bone explants were treated with hCM-Smurf1 to assess anti-resorptive effects. Proteomic analysis of the soluble and vesicular CM fractions identified key proteins involved in bone regeneration. Results CM from Smurf1-silenced MSCs significantly enhanced mineralization in vitro and bone formation in vivo. Preconditioning human osteoporotic MSCs with hCM-Smurf1 significantly increases in vitro mineralization, with levels comparable to those achieved with BMP2 treatment. Additionally, in ex vivo human bone cultures, treatment with hCM-Smurf1 significantly reduced RANKL expression without affecting OPG levels, indicating an anti-resorptive effect. In vivo, CM from Smurf1-silenced MSCs significantly increased bone formation in a rat ectopic model, and its local administration reduced trabecular bone loss by 50% in a post-menopausal osteoporotic mouse model after a single administration within just four weeks. Proteomic analysis revealed both soluble and vesicular fractions of hCM-Smurf1 were enriched with proteins essential for ossification and extracellular matrix organization, enhancing osteogenic differentiation. Conclusions The Smurf1-silenced MSCs' secretome shows potent osteogenic and anti-resorptive effects, significantly enhancing bone formation and reducing bone loss. This study provides compelling evidence for the therapeutic potential of Smurf1-silenced MSC-derived secretome as a non-toxic and targeted treatment for osteoporosis. These findings warrant further in vivo studies and clinical trials to validate its therapeutic efficacy and safety.https://doi.org/10.1186/s13287-025-04165-0OsteoporosisSmurf1SecretomeMesenchymal stem cells |
| spellingShingle | Alberto González-González Itziar Álvarez-Iglesias Daniel García-Sánchez Monica Dotta Ricardo Reyes Ana Alfonso-Fernández Alfonso Bolado-Carrancio Patricia Díaz-Rodríguez María Isabel Pérez-Núñez José Carlos Rodríguez-Rey Jesús Delgado-Calle Flor M. Pérez-Campo Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis Stem Cell Research & Therapy Osteoporosis Smurf1 Secretome Mesenchymal stem cells |
| title | Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis |
| title_full | Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis |
| title_fullStr | Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis |
| title_full_unstemmed | Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis |
| title_short | Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis |
| title_sort | paracrine activity of smurf1 silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis |
| topic | Osteoporosis Smurf1 Secretome Mesenchymal stem cells |
| url | https://doi.org/10.1186/s13287-025-04165-0 |
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