2022- PhD in Molecular and Regenerative medicine
2018- Master's Degree in Pharmaceutical Biotechnology cum Laude
RESEARCH, TEACHING, or OTHER INTERESTS
Cell Biology, Biochemistry, Genetics and Molecular Biology, Orthopedics and Sports Medicine
10
Scopus Publications
Scopus Publications
Challenges and Strategies in Hydrogel-Based Cartilage Regeneration Carola Cavallo, Emanuela Amore, Sara Carpentieri, Livia Roseti Gels, 2026 The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent these therapies from reaching the clinic. In view of these factors, we adopted a risk-based approach for this review, in line with the current legislative requirements in clinical translation and clinical trials. We identified the factors that could undermine patient safety or lead to poor outcomes. Then, we outlined solutions to remedy these problems that integrate hydrogel technology, clinical/pharmaceutical/surgical protocols, and post-operative follow-up. Upcoming studies should give priority to the development of hydrogel scaffolds modified to mimic cartilage’s mechanical and physicochemical properties, together with patient-specific features. Other crucial characteristics are host-tissue integration, long-lasting cartilage tissue regeneration, and a positive outcome. In parallel, to scale complex and costly innovations, efforts should focus on a harmonized, simplified legislative landscape, optimized standards, and established follow-up protocols. Getting through this “valley of death” between research and innovation is strategic for reaching the clinics and the largest number of patients.
Changes in Oxidative Stress, Inflammatory and Bone Metabolism Biomarkers Following Sulfurous Water Inhalation in Osteopenic Women Laura Gambari, Emanuela Amore, Livia Roseti, Sara Carpentieri, Claudio Ripamonti, Lucia Lisi, Paolo Spinnato, Giuliana Nervuti, Antonietta Gesuele, Susanna Naldi, Brunella Grigolo, Francesco Grassi International Journal of Molecular Sciences, 2026 Postmenopausal osteoporosis is an age-related condition in which estrogen deficiency drives low-grade inflammation and oxidative stress, disrupting the homeostatic balance between bone formation and resorption. Since osteopenia represents a critical intermediate stage, preventive strategies are essential to mitigate its progression. Preclinical studies suggest that hydrogen sulfide (H2S), a gaseous mediator with antioxidant properties, protects bone metabolism by supporting osteoblast function and suppressing osteoclast activity. Building on this evidence, we conducted the first exploratory clinical trial assessing the effects of inhalation therapy with sulfurous mineral waters on systemic biomarkers in postmenopausal women with osteopenia. Thirty-eight eligible participants underwent a daily inhalation of sulfurous waters (14.6 mg/L sulfide) for 12 consecutive days. Biomarkers of oxidative stress, inflammation, and bone turnover were assessed at baseline, immediately post-treatment, and five days after cessation in the serum of patients. The treatment was well tolerated and did not cause any early adverse effect. Serum H2S levels, measured in a subset of participants, significantly increased, confirming systemic bioavailability. Sulfurous water inhalation induced a marked change in oxidative stress, with malondialdehyde levels declining by up to 37% from baseline. Pro-inflammatory cytokines, particularly IL-8 and MIP-1α, were significantly decreased (up to 50–70%) at the end of the treatment. Reference bone turnover markers P1NP and CTX-1 did not show significant changes; however, BALP exhibited a significant increase, suggesting the activation of pathways linked to biomineralization. These findings provide preliminary human evidence that inhaled sulfurous waters enhance systemic H2S bioavailability and modulate redox and inflammatory pathways associated with bone remodeling in osteopenic women, supporting the rationale for further controlled pharmacodynamic investigations evaluating the potential of H2S in bone health.
Role of Dietary Glucosinolates and Isothiocyanate Derivatives in Osteoarthritis: Insights from a Narrative Review Giovanna Desando, Laura Gambari, Emanuela Amore, Giorgia Borciani, Sara Carpentieri, Francesco Grassi, Brunella Grigolo, Livia Roseti Applied Sciences Switzerland, 2025 Osteoarthritis is a common joint disease mainly characterized by inflammation and pain. Some promising approaches are aimed at combating the general mechanisms of osteoarthritis development and progression by targeting specific molecules. Although scientific and clinical communities remain skeptical regarding the efficacy of nutrition in managing human diseases, several products have been recognized as capable of improving health conditions and counteracting specific chronic and inflammatory musculoskeletal disorders such as osteoarthritis. The aim of this narrative review is to present the results obtained by a search through electronic databases on the effect of glucosinolates and their breakdown products, in particular isothiocyanates, in both the prevention and complementary therapy for osteoarthritis. Even if we found a few studies on this topic, some preclinical studies demonstrated an active role of these compounds in reducing inflammation, oxidative stress, and apoptosis. A beneficial effect of a diet rich in glucoraphanin, a glucosinolate derivative, has been associated with a lower risk of developing osteoarthritis in a proof-of-principle trial. To further advance this topic, it is essential to conduct additional preclinical studies to address existing research gaps, alongside more rigorous clinical investigations, especially long-term randomized controlled trials. These efforts should focus on determining the most effective type of glucosinolate and relative metabolites in counteracting osteoarthritis progression and identifying their dose–response behavior to assess both benefits and side effects associated with their oral intake.
Insights into Osteogenesis Induced by Crude Brassicaceae Seeds Extracts: A Role for Glucosinolates Laura Gambari, Eleonora Pagnotta, Luisa Ugolini, Laura Righetti, Emanuela Amore, Brunella Grigolo, Giuseppe Filardo, Francesco Grassi Nutrients, 2024 Background/Objectives: Crude extracts from the Brassica genus have recently emerged as promising phytochemicals for preventing bone loss. While the most documented evidence suggests that their general biological activity is due to glucosinolates’ (GLSs’) hydrolysis products, the direct activity of GLSs is beginning to be uncovered. However, the contribution of GLSs to the bone-sparing activity of crude Brassicaceae extracts has seldom been addressed. Here, we aimed to gain insights into this gap by studying in the same in vitro model of human osteogenesis the effect of two Brassica seed extracts (Eruca sativa and Lepidium sativum) obtained from defatted seed meals, comparing them to the isolated GLSs most represented in their composition, glucoerucin (GER) and glucotropaeolin (GTL), for Eruca sativa and Lepidium sativum, respectively. Methods: Osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was assessed by alizarin red staining assay and real-time PCR, respectively, evaluating mineral apposition and mRNA expression of specific osteogenic genes. Results: Both Brassica extracts and GLSs increased the osteogenic differentiation, indicating that the stimulating effect of Brassica extracts can be at least partially attributed to GLSs. Moreover, these data extend previous evidence of the effect of unhydrolyzed glucoraphanin (GRA) on osteogenesis to other types of GLSs: GER and GTL. Notably, E. sativa extract and GTL induced higher osteogenic stimulation than Lepidium sativum extract and GER, respectively. Conclusions: Overall, this study expands the knowledge on the possible application of Brassica-derived bioactive molecules as natural alternatives for the prevention and treatment of bone-loss pathologies.
Myoblast-Derived Galectin 3 Impairs the Early Phases of Osteogenesis Affecting Notch and Akt Activity Emanuela Amore, Vittoria Cenni, Manuela Piazzi, Michele Signore, Giulia Orlandi, Simona Neri, Stefano Biressi, Rosario Barone, Valentina Di Felice, Matilde Y. Follo, Jessika Bertacchini, Carla Palumbo Biomolecules, 2024 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.
Cannabinoids in the Inflamed Synovium Can Be a Target for the Treatment of Rheumatic Diseases Livia Roseti, Giorgia Borciani, Emanuela Amore, Brunella Grigolo International Journal of Molecular Sciences, 2024 The management of rheumatic diseases has noticeably changed in recent years with the development of targeted therapeutic agents, namely, biological disease-modifying antirheumatic drugs. Identifying essential signaling pathways and factors crucial for the development and progression of these diseases remains a significant challenge. Therapy could be used to delay the onset or reduce harm. The endocannabinoid system’s presence within the synovium can be identified as a suggested target for therapeutic interventions due to its role in modulating pain, inflammation, and joint metabolism. This review brings together the most pertinent information concerning the actions of the endocannabinoid system present in inflamed synovial tissue and its interaction with phytocannabinoids and synthetic cannabinoids, which can be used from a therapeutic perspective to minimize the inflammatory and pain processes typical of osteoarthritis and rheumatoid arthritis.
Glucoraphanin Increases Intracellular Hydrogen Sulfide (H2 S) Levels and Stimulates Osteogenic Differentiation in Human Mesenchymal Stromal Cell Laura Gambari, Marli Barone, Emanuela Amore, Brunella Grigolo, Giuseppe Filardo, Renato Iori, Valentina Citi, Vincenzo Calderone, Francesco Grassi Nutrients, 2022 Osteopenia and osteoporosis are among the most prevalent consequences of ageing, urging the promotion of healthy nutritional habits as a tool in preventing bone fractures. Glucosinolates (GLSs) are organosulfur compounds considered relatively inert precursors of reactive derivatives isothiocyanates (ITCs). Recent evidence suggests that GLSs may exert biological properties based on their capacity to release hydrogen sulfide (H2S). H2S-donors are known to exert anabolic function on bone cells. Here, we investigated whether a GLS, glucoraphanin (GRA) obtained from Tuscan black kale, promotes osteogenesis in human mesenchymal stromal cells (hMSCs). H2S release in buffer and intracellular H2S levels were detected by amperometric measurements and fluorimetric/cytofluorimetric analyses, respectively. Alizarin red staining assay and real-time PCR were performed to evaluate mineral apposition and mRNA expression of osteogenic genes. Using an in vitro cell culture model, our data demonstrate a sulforaphane (SFN)-independent osteogenic stimulation of GRA in hMSCs, at least partially attributable to H2S release. In particular, GRA upregulated the expression of osteogenic genes and enhanced mineral apposition while increasing intracellular concentrations of H2S. Overall, this study suggests the feasibility of using cruciferous derivatives as natural alternatives to chemical H2S-donors as adjuvant therapies in the treatment of bone-wasting diseases.
Identification of sclerostin as a putative new myokine involved in the muscle-to-bone crosstalk Maria Sara Magarò, Jessika Bertacchini, Francesca Florio, Manuela Zavatti, Francesco Potì, Francesco Cavani, Emanuela Amore, Ilaria De Santis, Alessandro Bevilacqua, Luca Reggiani Bonetti, Pietro Torricelli, Delphine B. Maurel, Stefano Biressi, Carla Palumbo Biomedicines, 2021 Bone and muscle have been recognized as endocrine organs since they produce and secrete “hormone-like factors” that can mutually influence each other and other tissues, giving rise to a “bone–muscle crosstalk”. In our study, we made use of myogenic (C2C12 cells) and osteogenic (2T3 cells) cell lines to investigate the effects of muscle cell-produced factors on the maturation process of osteoblasts. We found that the myogenic medium has inhibitory effects on bone cell differentiation and we identified sclerostin as one of the myokines produced by muscle cells. Sclerostin is a secreted glycoprotein reportedly expressed by bone/cartilage cells and is considered a negative regulator of bone growth due to its role as an antagonist of the Wnt/β-catenin pathway. Given the inhibitory role of sclerostin in bone, we analyzed its expression by muscle cells and how it affects bone formation and homeostasis. Firstly, we characterized and quantified sclerostin synthesis by a myoblast cell line (C2C12) and by murine primary muscle cells by Western blotting, real-time PCR, immunofluorescence, and ELISA assay. Next, we investigated in vivo production of sclerostin in distinct muscle groups with different metabolic and mechanical loading characteristics. This analysis was done in mice of different ages (6 weeks, 5 and 18 months after birth) and revealed that sclerostin expression is dynamically modulated in a muscle-specific way during the lifespan. Finally, we transiently expressed sclerostin in the hind limb muscles of young mice (2 weeks of age) via in vivo electro-transfer of a plasmid containing the SOST gene in order to investigate the effects of muscle-specific overproduction of the protein. Our data disclosed an inhibitory role of the muscular sclerostin on the bones adjacent to the electroporated muscles. This observation suggests that sclerostin released by skeletal muscle might synergistically interact with osseous sclerostin and potentiate negative regulation of osteogenesis possibly by acting in a paracrine/local fashion. Our data point out a role for muscle as a new source of sclerostin.
