Research Lines

Here you can find some detailed information about all of the units of our group.

Genomics Unit

PI: Ignacio Rego Pérez. The Genomics Unit main objective is the identification and study of the genetic and epigenetic basis of rheumatic diseases, mainly osteoarthritis. The Unit is part of RIER (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.

• The 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 Unit

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. The 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 Unit

Principal Investigators: Elena Fernández Burguera & Joana Magalhães.

The Regenerative Medicine Unit was established in 2007, being incorporated as a full-member of CIBER-BBN, as part of GBTTC-CHUAC, in the same year. Since 2016, the Unit is located in the main facilities of AE CICA-INIBIC. From 2017, the Unit is part of the international network IBEROS. Its main strategy is focused on the development of tools and technologies of regenerative medicine of musculoskeletal tissues as therapeutic solutions for osteoarthritic patients.

The main research lines of the Regenerative Medicine Unit are:

• Pre-clinical studies (in vitro and in vivo) using human primary cells (mainly chondrocytes and mesenchymal stromal cells) and small animal models (rat).

• Screening of new molecules with anti-inflammatory and chondrogenic effects and screening of biomaterials and delivery systems with application in cartilage lesions.

• Development of optical biomarkers for the early diagnosis of osteoarthritis.

• Study of hydrogen sulfide as a therapeutic target in rheumatic diseases. Our technological offer can be found here.

Cartilage Biology In Aging and OA Unit

PI: Beatriz Caramés Pérez. The 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 Unit

PI: Natividad Oreiro Vilar. The Clinical Research Unit 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 Unit

 PI: María Carmen de Andrés.

The Epigenetic Unit 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.