Mitochondrial DNA in Osteoarthritis Disease

[Abstract] Osteoarthritis (OA) is the most prevalent chronic joint disease, and we actually know that the activation of maladaptive responses to injury, including pro-inflammatory pathways, leads to the loss of normal joint function characterized by cartilage degradation, bone remodeling, osteophyte formation, and joint inflammation [1]. Recent insights into the epidemiology and impact of OA on patients have clearly established that OA is a severe disease of the whole joint as an organ, with large unmet medical needs. OA has a complex etiology that comprises the combination of multiple factors, including gender, age, occupation, trauma, body mass index, and genetics. Approximately, between 30 and 65% of the risk of OA is genetically determined [2] with evidence accumulated from different genome-wide association studies (GWAS) [3]. Most of these studies focused on nuclear genetic variants; however, over the last decade, evidence has accumulated for an association between specific mitochondrial DNA (mtDNA) genetic variants, called haplogroups, and different OA-related features, including prevalence, progression, and incidence [4].Instituto de Salud Carlos III; CIBERCB06/01/0040Instituto de Salud Carlos III; RETIC-RIER-RD16/0012/0002Instituto de Salud Carlos III; PRB2-ISCIII-PT17/0019/0014Instituto de Salud Carlos III; PI14/01254Instituto de Salud Carlos III; PI16/02124Instituto de Salud Carlos III; PI17/0021

Mitochondria and Mitophagy: Biosensors for Cartilage Degradation and Osteoarthritis

Editoria

Collaborative Multiobjective Evolutionary Algorithms in search of better Pareto Fronts. An application to trading systems

Technical indicators use graphic representations of data sets by applying various mathematical formulas to financial time series of prices. These formulas comprise a set of rules and parameters whose values are not necessarily known and depend on many factors: the market in which it operates, the size of the time window, and others. This paper focuses on the real-time optimization of the parameters applied for analyzing time series of data. In particular, we optimize the parameters of technical and financial indicators and propose other applications, such as glucose time series. We propose the combination of several Multi-objective Evolutionary Algorithms (MOEAs). Unlike other approaches, this paper applies a set of different MOEAs, collaborating to construct a global Pareto Set of solutions. Solutions for financial problems seek high returns with minimal risk. The optimization process is continuous and occurs at the same frequency as the investment time interval. This technique permits the application of non-dominated solutions obtained with different MOEAs simultaneously. Experimental results show that this technique increases the returns of the commonly used Buy \& Hold strategy and other multi-objective strategies, even for daily operations

Is osteoarthritis a mitochondrial disease?: what is the evidence

Final peer-reviewed manuscript[Abstract] Propose of review: To summarize the evidence that suggests that osteoarthritis (OA) is a mitochondrial disease. Recent findings: Mitochondrial dysfunction together with mtDNA damage could contribute to cartilage degradation via several processes such as: (1) increased apoptosis; (2) decreased autophagy; (3) enhanced inflammatory response; (4) telomere shortening and increased senescence chondrocytes; (5) decreased mitochondrial biogenesis and mitophagy; (6) increased cartilage catabolism; (7) increased mitochondrial fusion leading to further reactive oxygen species production; and (8) impaired metabolic flexibility. Summary: Mitochondria play an important role in some events involved in the pathogenesis of OA, such as energy production, the generation of reactive oxygen and nitrogen species, apoptosis, authophagy, senescence and inflammation. The regulation of these processes in the cartilage is at least partially controlled by retrograde regulation from mitochondria and mitochondrial genetic variation. Retrograde regulation through mitochondrial haplogroups exerts a signaling control over the nuclear epigenome, which leads to the modulation of nuclear genes, cellular functions and development of OA. All these data suggest that OA could be considered a mitochondrial disease as well as other complex chronic disease as cancer, cardiovascular and neurologic diseases.Instituto de Salud Carlos III; PI17/00210Instituto de Salud Carlos III; PI20/00614Instituto de Salud Carlos III; PI19/01206Instituto de Salud Carlos III; RETIC-RIER-RD16/0012/000

What did we learn from 'omics' studies in osteoarthritis

Review article[Abstract] Purpose of review: 'Omics' technologies developed for the massive analysis of the major biologically relevant molecules (genes, proteins, metabolites) have been applied to the study of osteoarthritis (OA) for more than a decade. Recent findings: 'Omics' studies have undoubtedly contributed to increase the knowledge on pathogenic processes related with OA and have provided hundreds to thousands of molecules that might have a putative biomarker utility for this disease. Summary: This review describes the most recent 'omics' studies in OA research, their conclusions, and discuss those remaining challenges. Still many validation studies must be performed in large and well-characterized cohorts for the translation of the findings from 'omics' strategies to clinical applications. The development of tools for the intelligent integration of 'omics' data with clinical and imaging information is also mandatory to take full profit of the work that has been already performed.Instituto de Salud Carlos III; PI14/01707Instituto de Salud Carlos III; PI14/01254Instituto de Salud Carlos III; PI16/02124Instituto de Salud Carlos III; CIBERCB06/ 01/0040Instituto de Salud Carlos III; RETIC-RIER-RD12/0009/0018Instituto de Salud Carlos III; PT13/000

Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient’s genetic profile

Buildings environmental impact assessment: simulation of textures

To study the construction as modifying of the environment and by so much as aesthetic attribute of the scene should know in what aspect influences. The physical resources of the landscape will be very seemed before and after the incorporation of a project (quality of content). Therefore they will be mainly the new composition of the elements (communicative quality) and the aesthetic resources (quality aesthetics) on those which will influence the constructions. The different points of view election will remain settled with the simulation by infographic photocomposition. The visual and aesthetic aspect of any object is defined by their characteristic of color, form, line and texture. It could be also added any elements of compositive reference as are its scale and being tried to stages, as is the case of the landscape, its spatial character. In this article we will center ourselves in one of these attributes: the texture. The different textures vision is crucial in the communication. The simulation of the landscapte has suffered a great impulse with the treatment of the photograph. This method admits various alternatives. It can be analyzed the taken image of the reality such which, or deducting some of its parts, adding some other element originating from the same or of other scene, or including constructions designed in CAD. The great advance, for the investigation of the visual perception, is procured in the composition using the landscape as fund and a construcion created through a design program attended by ordering. This step supposes great alternatives variability and a rapid generation of the same. Settled the great problem to obtain to compatibilize the points of view of the panorama and of the superposed performance and climinated by photographic treatment the properties of the surfaces that tent to be smooth and metalized brilliants. The reflections and conclusions of the texture emerge with speed. They are analyzed in the study the different simulations with different textures

Tuning interfacial domain walls in GdCo/Gd/GdCo′ spring magnets

Under the terms of the Creative Commons Attribution License 3.0 (CC-BY).-- et al.Spring magnets based on GdCo multilayers have been prepared to study the nucleation and evolution of interfacial domain walls (iDWs) depending on layer composition and interlayer coupling. GdCo alloy compositions in each layer were chosen so that their net magnetization aligns either with the Gd (Gd35Co65) or Co(Gd11Co89) sublattices. This condition forces an antiparallel arrangement of the layers' net magnetization and leads to nucleation of iDWs above critical magnetic fields whose values are dictated by the interplay between Zeeman and exchange energies. By combining x-ray resonant magnetic scattering with Kerr magnetometry, we provide detailed insight into the nucleation and spatial profile of the iDWs. For strong coupling (GdCo/GdCo′ bilayer), iDWs are centered at the interface but with asymmetric width depending on each layer magnetization. When interlayer coupling is weakened by introducing a thin Gd interlayer, the exchange spring effect becomes restricted to a lower temperature and field range than observed in the bilayer structure. Due to the ferromagnetic alignment between the high magnetization Gd35Co65 layer and the Gd interlayer, the iDW shrinks and moves into the lower exchange Gd interlayer, causing a reduction of iDW energy.Work supported by Spanish Ministerio de Economía y Competitividad (MINECO) under grant FIS2013-45469 and Spanish Ministerio de Ciencia e Innovacion (MICINN) under grant FIS2008-06249. Work at Argonne was supported by the U.S. Department of Energy, Office of Science, under Contract No. DE-AC02-06CH11357.Peer Reviewe

Leukocyte telomere length in patients with radiographic knee osteoarthritis

Brief communication[Abstract] Relative mean telomere sequence amount was determined by quantitative PCR (qPCR) of peripheral blood leukocyte (PBL) samples obtained at recruitment (n = 310) from individuals from the Osteoarthritis (OA) Initiative consortium. Knees were radiologically evaluated according to the Kellgren–Lawrence (KL) score, ranging from 0 to 4, considering a KL grade ≥ 2 as radiographic evidence of OA (n = 124). Telomere size decreased as baseline KL score increased, being significantly shorter in subjects with KL ≥2 (Mann–Whitney U‐test, P < 0.0001). PBL telomere size was also associated with age, hypertension, body mass index (BMI) and waist circumference. Nevertheless, logistic regression analysis showed that PBL telomere size was a consistent risk factor for concurrent knee OA, independent of these health parameters. Shorter PBL telomeres may indicate a premature aging status which enhances chondrocyte senescence and degenerative joint disease.Instituto de Salud Carlos III; PI17/01987Instituto de Salud Carlos III; PI16/0212

Mitochondrial genetics and epigenetics in osteoarthritis

Review[Abstract] During recent years, the significant influence of mitochondria on osteoarthritis (OA), the most common joint disease, has been consistently demonstrated. Not only mitochondrial dysfunction but also mitochondrial genetic polymorphisms, specifically the mitochondrial DNA haplogroups, have been shown to have an important influence on different OA-related features, including the prevalence, severity, incidence, and progression of the disease. This influence could probably be mediated by the role of mitochondria in the regulation of different processes involved in the pathogenesis of OA, such as energy production, the generation of reactive oxygen and nitrogen species, apoptosis, and inflammation. The regulation of these processes is at least partially controlled by the bi-directional communication between the nucleus and mitochondria, which permits the regulation of adaptation to a wide range of stressors and the maintenance of cellular homeostasis. This bi-directional communication consists of an “anterograde regulation” by which the nucleus regulates mitochondrial biogenesis and activity and a “retrograde regulation” by which both mitochondria and mitochondrial genetic variation exert a regulatory signaling control over the nuclear epigenome, which leads to the modulation of nuclear genes. Throughout this mini review, we will describe the evidence that demonstrates the profound influence of the mitochondrial genetic background in the pathogenesis of OA, as well as its influence on the nuclear DNA methylome of the only cell type present in the articular cartilage, the chondrocyte. This evidence leads to serious consideration of the mitochondrion as an important therapeutic target in OA.Instituto de Salud Carlos III; CIBERCB06/01/0040Instituto de Salud Carlos III; RETIC-RIER-RD16/0012/0002Instituto de Salud Carlos III; PRB2-ISCIII-PT17/0019/0014Instituto de Salud Carlos III; PI14/01254Instituto de Salud Carlos III; PI16/02124Instituto de Salud Carlos III; PI17/00210Instituto de Salud Carlos III; (CPII17/00026