Facultad de Ciencias de la Salud

Osteoarthritis (OA) is a degenerative condition of the articular cartilage with chronic low-grade inflammation. Monocytes have a fundamental role in the progression of OA, given their implication in inflammatory responses and their capacity to differentiate into bone-resorbing osteoclasts (OCLs). This observational–experimental study attempted to better understand the molecular pathogenesis of OA through the examination of osteoclast progenitor (OCP) cells from both OA patients and healthy individuals (25 OA patients and healthy samples). The expression of osteoclastogenic and inflammatory genes was analyzed using RT-PCR. The OA monocytes expressed significantly higher levels of CD16, CD115, TLR2, Mincle, Dentin-1, and CCR2 mRNAs. Moreover, a flow cytometry analysis showed a significantly higher surface expression of the CD16 and CD115 receptors in OA vs. healthy monocytes, as well as a difference in the distribution of monocyte subsets. Additionally, the OA monocytes showed a greater osteoclast differentiation capacity and an enhanced response to an inflammatory stimulus. The results of this study demonstrate the existence of significant differences between the OCPs of OA patients and those of healthy subjects. These differences could contribute to a greater understanding of the molecular pathogenesis of OA and to the identification of new biomarkers and potential drug targets for OA.

The use of mesenchymal stem cells constitutes a promising therapeutic approach, as it has shown beneficial effects in different pathologies. Numerous in vitro, pre-clinical, and, to a lesser extent, clinical trials have been published for osteoarthritis. Osteoarthritis is a type of arthritis that affects diarthritic joints in which the most common and studied effect is cartilage degradation. Nowadays, it is known that osteoarthritis is a disease with a very powerful inflammatory component that affects the subchondral bone and the rest of the tissues that make up the joint. This inflammatory component may induce the differentiation of osteoclasts, the bone-resorbing cells. Subchondral bone degradation has been suggested as a key process in the pathogenesis of osteoarthritis. However, very few published studies directly focus on the activity of mesenchymal stem cells on osteoclasts, contrary to what happens with other cell types of the joint, such as chondrocytes, synoviocytes, and osteoblasts. In this review, we try to gather the published bibliography in relation to the effects of mesenchymal stem cells on osteoclastogenesis. Although we find promising results, we point out the need for further studies that can support mesenchymal stem cells as a therapeutic tool for osteoclasts and their consequences on the osteoarthritic joint.

One of the best consolidated paradigms in vascular pharmacology is that an uncontrolled excess of oxidizing chemical species causes tissue damage and loss of function in the endothelial and subendothelial layers. The fact that high-density lipoproteins play an important role in preventing such an imbalance is integrated into that concept, for which the expression and activity of paraoxonases is certainly crucial. The term paraoxonase (aryldialkyl phosphatase, EC 3.1.8.1) encompasses at least three distinct isoforms, with a wide variation in substrate a nity, cell and fluid localization, and biased expression of polymorphism. The purpose of this review is to determine the interactions that paraoxonase 1 has with nitric oxide synthase, its reaction product, nitric oxide (nitrogen monoxide, NO), and its derived reactive species generated in an oxidative medium, with a special focus on its pathological implications.

Ellagic acid is a common metabolite present in many medicinal plants and vegetables. It is present either in free form or as part of more complex molecules (ellagitannins), which can be metabolized to liberate ellagic acid and several of its metabolites, including urolithins. While ellagic acidʼs antioxidant properties are doubtless responsible for many of its pharmacological activities, other mechanisms have also been implicated in its various effects, including its ability to reduce the lipidemic profile and lipid metabolism, alter pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, interleukin-6), and decrease the activity of nuclear factor-κB while increasing nuclear factor erythroid 2-related factor 2 expression. These events play an important role in ellagic acidʼs anti-atherogenic, anti-inflammatory, and neuroprotective effects. Several of these activities, together with the effect of ellagic acid on insulin, glycogen, phosphatases, aldose reductase, sorbitol accumulation, advanced glycation end-product formation, and resistin secretion, may explain its effects on metabolic syndrome and diabetes. In addition, results from recent research have increased the interest in ellagic acid, both as a potential protective agent of the liver and skin and as a potential anticancer agent, due to the specific mechanisms affecting cell proliferation, apoptosis, DNA damage, and angiogenesis and its aforementioned anti-inflammatory properties. Taken together, these effects make ellagic acid a highly interesting compound that may contribute to different aspects of health; however, more studies are needed, especially on the compoundʼs pharmacokinetic profile. In this review, we selected papers published from 2005 to the present.