Elena Nebot

It has been proposed that muscle influences adjacent bones, but the mechanisms by which muscle regulates bone physiology are not fully understood. Sciatic denervation is an experimental model that induces both skeletal muscle atrophy and osteoporosis. Therefore, the aim of this study was to analyze, in this animal model, expression of myokines in the atrophic soleus and its possible effect on changes in tibia microarchitectural parameters in 9-12 weeks old male rats. For this purpose, soleus insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), fibronectin type III domain-containing 5 (FNDC5), fibroblast growth factor 21 (FGF21) mRNA, and miR-150, were measured by real-time PCR and tibia microarchitecture was assessed 3, 7, and 14 days after sciatic denervation. Denervation induced soleus atrophy and decreased trabecular bone density, thickness, and number. In the atrophic soleus, there was an increase in IL-6, IGF-1, and FGF21 mRNA, with a decrease in FNDC5 mRNA and miR-150 levels. No correlation between soleus IL-6 or IGF-1 and trabecular bone parameters was found. However, FGF21 was negatively correlated with trabecular bone mineral content, whereas FNDC5 mRNA and miR-150 levels were positively correlated. These data suggest that modifications in FGF21, FNDC5, and miR-150 during muscle atrophy may mediate muscle-bone crosstalk and contribute to bone loss, while IL-6 and IGF-1 do not seem to play a predominant role.

Edible flowers have garnered increasing attention due to their high content of bioactive compounds, making them promising candidates for biomedical and functional food applications. This work evaluated the metabolomic data of fresh Rosa x hybrida petals, revealing seven types of metabolites, including amino acids, organic acids, vitamins, sugars, phenolic acids, and flavonoids. Notably, quercetin, kaempferol and their derivatives were the main flavonoids determined. Furthermore, in vitro studies were conducted to evaluate the potential antiproliferative effects against triple-negative breast cancer (TNBC). Thus, the methanolic extract derived from Rosa x hybrida petals demonstrated significant antitumoral activity against both sensitive and resistant TNBC cells, as evidenced by reduced MTT metabolization, colony formation, and wound healing activity. Furthermore, the cell death mechanism associated with the petal extract was studied. The antiproliferative activity was mediated by reactive oxygen species generation, triggering cell death mechanisms such as apoptosis and autophagy. In conclusion, these results propose Rosa x hybrida could be a new tool for nutraceuticals and functional food production.

Denervation-induced muscle atrophy is a frequent cause of skeletal muscle diseases. However, the role of the most important muscle growth factor, insulin-like growth factor (IGF-1), in this process is poorly understood. IGF-1 activity is controlled by six IGF-1 binding proteins (IGFBPs). In skeletal muscle, IGFBP-5 seems to have an important role in atrophic processes. Furthermore, pappalysins (PAPP-A) modulate muscle growth by increasing IGF-1 bioavailability through IGFBP cleavage. We aimed to study the time-dependent changes in the IGF1-IGFBP5-PAPP system and its regulators in gastrocnemius muscle after sciatic denervation. Gastrocnemius atrophy and overexpression of IGF-1 was observed from day 3 post-denervation. The proteolytic factors measured were elevated from day 1 post-denervation onwards. Expression of both IGFBP-5 and pappalysins were increased on days 1 and 3. Subsequently, on days 7 to 14 pappalysins returned to control levels while IGFBP-5 remained elevated. The ratio IGFBP-5/PAPP-A was correlated with the main proteolytic markers. All data suggest that the initial increase of pappalysins could facilitate the IGF-1 action on muscle growth, whereas their subsequent decrease could lead to further muscle wasting.

The association of obesity with changes in bone mass is not clear. Obese individuals tend to have an increased bone mineral density, but other studies have shown that obesity is a major risk factor for fractures. The mechanisms of bone response during a weight loss therapy as well as the possible osteoprotective effect of exercise should be analyzed. The aim of this study was to test the effects of a weight-loss program based on the combination of caloric restriction and/or a mixed training protocol on different parameters of bone morphology and functionality in a DIO rat model. Three stages were established over a 21-week period (obesity induction 0–12 w, weight loss intervention 12–15 w, weight maintenance intervention 15–21 w) in 88 male Sprague Dawley rats. Bone microarchitecture, total mineral and elemental composition, and bone metabolism parameters were assessed. Weight loss interventions were associated to healthy changes in body composition, decreasing body fat and increasing lean body mass. On the other hand, obesity was related to a higher content of bone resorption and inflammatory markers, which was decreased by the weight control interventions. Caloric restriction led to marked changes in trabecular microarchitecture, with a significant decrease in total volume but no changes in bone volume (BV). In addition, the intervention diet caused an increase in trabeculae number and a decrease in trabecular spacing. The training protocol increased the pore diameter and reversed the changes in cortical porosity and density of BV induced by the high protein diet at diaphysis level. Regarding the weight-maintenance stage, diminished SMI values indicate the presence of more plate-like spongiosa in sedentary and exercise groups. In conclusion, the lifestyle interventions of caloric restriction and mixed training protocol implemented as weight loss strategies have been effective to counteract some of the deleterious effects caused by a dietary induction of obesity, specifically in trabecular bone morphometric parameters as well as bone mineral content.

Although Paget’s disease of bone (PDB) is the second most common metabolic bone disease, there is only limited information about the microarchitecture of affected bones. Therefore, the aim of this study was to determine cortical and trabecular bone properties in clinically relevant locations by microcomputed tomography (µCT). Ten femora and ten tibiae affected by Paget’s disease taken from the Natural History Museum Vienna were compared to 13 femora and 10 tibiae of non-affected body donors. Digitization of the cortical and trabecular bone microarchitecture was performed with an X-ray-based µCT scanner. Additionally, semi-quantitative gradings of trabecular and cortical architectural parameters of the femora and the tibiae were generated. Microcomputed tomography images showed changes in the thickness of cortices, cortical porosity, and trabecularization of cortical structures. Moreover, severe disorganization of trabecular structures, trabecular defects, and thickening of (remaining) trabeculae were detected. Numerical cortical analyses showed lower total bone volume (BV) and lower BV in the outer region (66–100%) (− 36%, p = 0.004, and − 50%, p < 0.001, respectively), lower total volume (TV) in the outer region (66–100%) (− 42%, p < 0.001), lower total bone volume fraction (BV/TV) and BV/TV in the outer region (66–100%) (− 23%, and − 12%, p < 0.001, respectively), higher BV and TV in the middle region (33–66%) and higher BV/TV in the inner region (0–33%) (123%, p = 0.011, 147%, p = 0.010, and 33%, p = 0.025, respectively) in Pagetic compared to non-affected bones. Trabecular analyses showed higher BV/TV (96%, p = 0.008) and Tb.Th (43%, p = 0.004) in Pagetic compared to non-affected bones. There is a major and consistent structural alteration of PDB at cortical and trabecular sites in weight-bearing long bones. Our findings are relevant for the differential diagnosis of PDB and for the pathogenesis of associated complications, since the disorder produces abnormalities in the structure that might lead to bone fragility.

Metabolic syndrome (MetS) is a group of related metabolic alterations that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). Several lifestyle interventions based on dietary treatment with functional ingredients and physical activity are being studied as alternative or reinforcement treatments to the pharmacological ones actually in use. In the present experiment, the combined treatment with mung bean (Vigna radiata), a widely used legume with promising nutritional and health benefits that was included in the experimental diet as raw or 4 day-germinated seed flour, and aerobic interval training protocol (65–85% VO₂ max) has been tested in lean and obese Zucker rats following a 2 × 2 × 2 (2 phenotypes, 2 dietary interventions, 2 lifestyles) factorial ANOVA (Analysis of Variance) statistical analysis. Germination of V. radiata over a period of four days originated a significant protein hydrolysis leading to the appearance of low molecular weight peptides. The combination of 4 day-germinated V. radiata and aerobic interval training was more efficient compared to raw V. radiata at improving the aerobic capacity and physical performance, hepatic histology and functionality, and plasma lipid parameters as well as reverting the insulin resistance characteristic of the obese Zucker rat model. In conclusion, the joint intervention with legume sprouts and aerobic interval training protocol is an efficient treatment to improve the alterations of glucose and lipid metabolism as well as hepatic histology and functionality related to the development of NAFLD and the MetS.