Research Lines
GENOMICS
Principal Investigator: Ignacio Rego Pérez.
Genomics Unit main objective is the identification and study of the genetic and epigenetic basis of rheumatic diseases, RIER mainly osteoarthritis. The Unit is part of (Inflammation and Rheumatic Diseases), from the Spanish Institute of Health (ISCIII), and, more specifically, is dedicated to the study of the mitochondrial genome, as a potential candidate biomarker of disease, in:
- The incidence, progression and severity of osteoarthritis, through the identification of mitochondrial genetic variants, using advanced sequencing techniques, in different prospective and retrospective cohorts of OA patients.
- Epigenome of osteoarthritis, through the design of cellular models that permit, on one hand, to evaluate the impact of mitochondrial genome in the modulation of the epigenetic profile of chondrocytes and, on the other hand, to identify epigenetic markers that allow to distinguish different osteoarthritis phenotypes.
PROTEOMICS
PI: Cristina Ruiz Romero.
The Proteomics Unit started its activities in 2004. Since 2006, when it was incorporated as an Associated Node to the National Proteomics Institute (ProteoRed), from the Spanish Institute of Health (ISCIII), being the only research group from the Autonomic Region of Galicia belonging to this network of proteomics facilities. As such, it is also the core of the Proteomics Platform of INIBIC. This support platform is responsible of providing services and counseling for the development of proteomic studies by other national and international research groups.
This Unit also participates in the worldwide Human Proteome Project, leading its initiative on Rheumatic and Autoimmune Diseases (RAD-HPP). The research activities of this Unit are focused on the use of proteomic approaches for the study of the pathogenesis of rheumatic diseases and the search of novel protein biomarkers with potential clinical application.
The main research lines of the Proteomics Unit are:
• Discovery and validation of novel protein biomarkers useful to improve the diagnosis, prognosis and/or monitoring of rheumatic diseases, with a special focus on osteoarthritis, rheumatoid arthritis and psoriatic arthritis.
• Search of proteins with value to predict response to therapy in rheumatic diseases.
• Studies on osteoarthritis pathogenesis and therapy by proteomics strategies: evaluation of the articular cartilage degradation process or analysis of the chondrogenic differentiation of mesenchymal stromal cells.
• Development and implementation of cutting-edge proteomic technologies with clinical application for the study of rheumatic pathologies (e.g. mass spectrometry imaging, protein microarrays and immunoaffinity strategies coupled to mass spectrometry).
REGENERATIVE MEDICINE
Principal Investigators: Mercedes Fernández-Moreno & Tamara Hermida-Gómez.
The Regenerative Medicine Unit was established in 2007, being incorporated as a full-member of CIBER-BBN. Since 2016, the Unit is located in the main facilities of Centro Interdisciplinar de Quimica e Bioloxia (CICA). Its main strategy is focused on the development of tools and technologies of regenerative medicine of musculoskeletal tissues as therapeutic solutions for osteoarthritic (OA) patients.
Recently, with the CICA reorganization, our group was include in BMed CICA (Biomedicine) Grupo de Investigación en Reumatalogia y Salud (GIR-S) (https://cica.udc.gal/group/gir-s/)
Our objectives including the application of basic research results in medicine, in order to know why rheumatic diseases develop and find new forms of diagnosis, prognosis, prevention and treatment of OA patients.
In 2021 the new concept Advance Therapies was introduced. From this date, we have been developed in the use of advanced cellular therapies focused in the mitochondria as a therapeutic target for OA pathology, both from the point of view of laboratory research (in vitro models) and from that of trials using in vivo models.
The main research lines of the Regenerative
- Test the mitochondrial application as a possible therapeutic option in OA models in vitroand in vivo.
- Pre-clinical studies (in vitroand in vivo) using human primary cells (mainly chondrocytes and mesenchymal stromal cells) and small animal models (mouse and rat).
- Develop of cellular models based in transmitochondrial cybrids to evaluated the mitochondrial role of mitochondrial behavior under different conditions
- Metabolic analysis using cellular models or primary cells.
- Test the effect of natural compound over the human osteoarthritic chondrocytes (in vitromodels) or using in vivo
- Screening of new molecules with anti-inflammatory and chondrogenic effects and with application in cartilage lesions. Study of hydrogen sulfide as a therapeutic target in rheumatic diseases.
Selected publications:
- Durán-Sotuela, A., Fernandez-Moreno, M., et al. A meta-analysis and a functional study support the influence of mtDNA variant m.16519C on the risk of rapid progression of knee osteoarthritis. 2023. Ann Rheum Dis. PMID: 37024296.
- Flórez-Fernández, N., Vaamonde-García, C. et al., Relevance of the Extraction Stage on the Anti-Inflammatory Action of Fucoidans. 2023. Pharmaceutics PMID: 36986669.
- Vaamonde-García, C., Capelo-Mera, E., et al. In Vitro Study of the Therapeutic Potential of Brown Crude Fucoidans in Osteoarthritis Treatment. 2022. Int J Mol Sci. PMID: 36430716.
- Scotece, M., Vaamonde-García, C. et al., mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model. 2022. Aging. PMID: 35779570.
- Fernández-Moreno, M., Rego-Pérez, I and Blanco, FJ. Is osteoarthritis a mitochondrial disease? What is the evidence. 2022. Curr Opin Rheumatol. PMID: 34750310.
- María Piñeiro-Ramil, M., F Burguera, E., et al., Reduced Levels of H2S in Diabetes-Associated Osteoarthritis Are Linked to Hyperglycaemia, Nrf-2/HO-1 Signalling Downregulation and Chondrocyte Dysfunction. 2022. Antioxidants (Basel). PMID: 35453313.
- Vaamonde-García, C., Flórez-Fernández, N., et al., Study of fucoidans as natural biomolecules for therapeutical applications in osteoarthritis. 2021. Carbohydr Polym. PMID: 33593565.
- Dalmao-Fernández, A., Hermida-Gómez, T., et al., Mitochondrial DNA from osteoarthritic patients drives functional impairment of mitochondrial activity: a study on transmitochondrial cybrids. 2021. Cytotherapy. PMID: 33727013.
- Blanco, F.J and Fernández-Moreno, M. Mitochondrial biogenesis: a potential therapeutic target for osteoarthritis. 2020. Osteoarthritis Cartilage. PMID: 32417558.
- Vaamonde-García, C., F Burguera, E. et al., Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis. 2020. Int J Mol Sci. PMID: 33050005.
- Dalmao-Fernández, A., Lund, J., et al., Impaired Metabolic Flexibility in the Osteoarthritis Process: A Study on Transmitochondrial Cybrids. 2020. Cells. PMID: 32230786.
- Fernández-Moreno, M., Hermida-Gómez, T., et al., Generating Rho-0 Cells Using Mesenchymal Stem Cell Lines. 2016. PLoS One. PMID: 27764131.
CARTILAGE BIOLOGY
PI: Beatriz Caramés Pérez.
Cartilage Biology Unit was established in 2012, when Dra. Beatriz Caramés was appointed as Miguel Servet Senior Scientist, by the National Institute of Health Carlos III (ISCIII). The Unit’s research focusses on discovering and functionally characterizing cellular mechanisms of articular cartilage dysregulated in aging and osteoarthritis (OA). Chondrocyte homeostasis checkpoints represent opportunities for targeting cartilage damage and OA initiation.
This strategy is addressed by the following research priorities:
• Functional characterization of the mechanisms related to aging and the degradation of articular cartilage in osteoarthritis.
• Consequences of metabolic diseases on articular cartilage homeostasis in osteoarthritis.
• Identification of new therapeutic targets aimed at preventing and / or delaying joint aging and osteoarthritis.
Selected publications:
• Vinatier C, Domínguez E, Guicheux J, Caramés B. Role of the Inflammation-Autophagy-Senescence Integrative Network in Osteoarthritis. Front Physiol. 2018, 25;9:706.
• Ribeiro M, López de Figueroa P, Nogueira-Recalde U, Centeno A, Mendes AF, Blanco FJ, Caramés B. Diabetes-accelerated experimental osteoarthritis is prevented by autophagy activation. Osteoarthritis Cartilage. 2016;24:2116-2125.
• Ribeiro M, López de Figueroa P, Blanco FJ, Mendes AF, Caramés B. Insulin decreases autophagy and leads to cartilage degradation. Osteoarthritis Cartilage. 2016;24:731-9.
• Caramés B, Olmer M, Kiosses WB, Lotz MK. The relationship of autophagy defects to cartilage damage during joint aging in a mouse model. Arthritis Rheumatol. 2015;67:1568-76.
• López de Figueroa P, Lotz MK, Blanco FJ, Caramés B. Autophagy activation and protection from mitochondrial dysfunction in human chondrocytes. Arthritis Rheumatol. 2015;67:966-76.
• Caramés B, Hasegawa A, Taniguchi N, Miyaki S, Blanco FJ, Lotz M. Autophagy activation by rapamycin reduces severity of experimental osteoarthritis. Ann Rheum Dis. 2012;71:575-81.
• Caramés B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 2010;62:791-801.
• Lotz MK, Caramés B. Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA. Nat Rev Rheumatol. 2011;7:579-87.
CLINICAL RESEARCH
Principal Investigator: Natividad Oreiro Vilar.
Another of our GIR Research Lines is The Clinical Research which started its activity more than 20 years ago. Its main goal is to promote the advancement in clinical and therapeutic research areas, contributing to the understanding and treatment of rheumatic diseases.
The Unit main goals are:
• Participation in Clinical Trials, from phases Ib to IV and observational studies in different rheumatic pathologies (inflammatory diseases, vasculitis, connective pathologies, microcrystalline arthropathies, osteoarthritis and osteoporosis).
• Promote Independent Research Projects in rheumatic diseases.
• Follow-up of cohorts of patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and osteoarthritis.
• Participation in National and International Competitive Research Projects.
EPIGENETICS
PI: María Carmen de Andrés.
Another of our GIR Research Lines is Epigenetic Unit, that was established in 2019, when Dra. Mª Carmen de Andrés González was appointed as Miguel Servet Researcher by the National Institute of Health Carlos III (ISCIII). The main focus of this unit is the identification of new drugs and/or nutraceutical compounds with proven efficacy in cartilage repair and, critically, demonstrating the potential for epigenetic and nutraceutical intervention in OA, providing a step-change in current OA clinical intervention strategies.
The main research line of the Epigenetics Unit is to explore two new avenues as targeted therapy in OA: A chemical approach by using epigenetic modifiers (e.g. histone methyltransferases, lysine demethylases) and a nutraceutical approach by using natural derivatives (e.g. extra virgin olive oil (EVOO) and its component polyphenols, and marine ω-3 fatty acids supplements particularly the bioactive fatty acids eicosapentaenoic acid (EPA), docopentaenoic acid (DPA) and docosahexaenoic acid (DHA).
Selected publications:
Takahashi A, de Andrés MC, et al. DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes. Sci Rep. 2017;7(1):7771.
- de Andrés et al. Demethylation of an NF-κB enhancer element orchestrates iNOS induction in osteoarthritis and is associated with altered chondrocytic cell cycle. Osteoarthritis Cartilage. 2016;24(11):1951-60.
- Takahashi A, de Andrés MC, et al. Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1946-54.
- de Andrés MC et al. Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate. Arthritis Res Ther. 2015;17:233.
- Alvarez K, de Andrés MC et al. Effects of hypoxia on anabolic and catabolic gene expression and DNA methylation in OA chondrocytes. BMC Musculoskelet Disord. 2014;15:431.
- Imagawa K, de Andrés MC et al. Association of reduced type IX collagen gene expression in human osteoarthritic chondrocytes with epigenetic silencing by DNA hypermethylation. Arthritis Rheumatol. 2014;66(11):3040-51.
- Hashimoto K, Otero M, Imagawa K, de Andrés MC et al. Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites. J Biol Chem. 2013;288(14):10061-72.
- de Andrés MC et al. Epigenetic regulation during fetal femur development: DNA methylation matters. PLoS One. 2013;8(1):e54957.
- de Andrés MC et al. Loss of methylation in CpG sites in the NF-κB enhancer elements of inducible nitric oxide synthase is responsible for gene induction in human articular chondrocytes. Arthritis Rheum. 2013;65(3):732-42.
TEAM MEMBERS
If you want information about each of the members of our group and subgroups, consult the “Team” section of our website:
