Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN’s multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with learning and memory deficit. Murine model of lupus induced by pristane in BALB/c mice is an experimental model that resembles some clinical and immunological SLE pathogenesis. Nevertheless, there is no experimental evidence that relates this model to cognitive dysfunction associated with NR2A/2B relative expression. To evaluate cognitive impairment related to memory deficits in a murine model of lupus induced by pristane in BALB/c mice related to mRNA relative expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition in a behavioral test with the use of Barnes maze. A total of 54 female BALB/c mice 8–12 weeks old were included into 3 groups: 7 and 12 weeks using pristane alone (0.5 mL of pristane) by a single intraperitoneal (i.p.) injection. A control group (single i.p. injection of 0.5 mL NaCl 0.9%) and pristane plus LPS exposure using single i.p. pristane injection and LPS of E. coli O55:B5, in a dose of 3mg/kg diluted in NaCl 0.9% 16 weeks post-pristane administration. To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/2B subunits (GAPDH as housekeeping gene) with SYBR green quantitative reverse transcription polymerase chain reaction and 2^-ΔΔC_T method were determined in the groups. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7 and 12 weeks of treatment and it is related to learning and memory disturbance assayed by Barnes maze. This is the first report using the murine model of lupus induced by pristane that analyzes the NMDA subunit receptors, finding a downregulation of NR2A subunit related to learning and memory disturbance being more evident when they were exposed to LPS.

The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser inPPARGC1Aand Pro12Ala inPPARG2with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphismPPARGC1Adistribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly− phenotype. Subjects withPPARG2Ala− phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser inPPARGC1Aand 12Pro inPPARG2represents a reduced metabolic risk profile, even when the adiposity indexes are increased.

Leptin has a prominent role in the development and maintenance of acute and chronic inflammatory states such as rheumatoid arthritis (RA) and obesity. Nevertheless, the association of serum leptin (sLep) and soluble leptin receptor (sLepR) in RA pathogenesis has not been clarified. The purpose of this study was to evaluate the association of sLep, sLepR and leptin production indexes such as sLep/fat mass ratio with clinical activity and biomarkers and anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA compared with body mass index (BMI) matched control subjects. We included 64 RA patients and 66 controls matched for age, gender and BMI. Subjects were evaluated for BMI, fat mass distribution, sLep, sLepR, sLep/fat mass ratio and sLepR/fat mass ratio. Patients were evaluated for clinical activity and anti-CCP antibodies. We found two or three fold increased sLep levels, sLep/sLepR ratio and sLep/fat mass ratio in obese anti-CCP positive RA patients vs. controls. Partial correlations showed that anti-CCP antibodies were correlated with sLep/fat mass ratio (partial r = 0.347, P = 0.033) after adjustment for age, subcutaneous adipose tissue and fat mass. In preobese and obese RA patients there is and increased production of sLep according to anti-CCP positivity. This phenomenon suggests there is an additive effect of chronic inflammation resulting from RA and obesity in which leptin favors the humoral response against citrullinated proteins. In summary, the data observed in our study suggests sLep could be a surrogate marker of chronicity and humoral immunity in RA in the presence of obesity.

Metabolic syndrome (MetS) is a group of physiological abnormalities characterized by obesity, insulin resistance (IR), and hypertriglyceridemia, which carry the risk of developing cardiovascular disease (CVD) and type 2 diabetes (T2D). Immune and metabolic alterations have been observed in MetS and are associated with autoimmune development. Systemic lupus erythematosus (SLE) is an autoimmune disease caused by a complex interaction of environmental, hormonal, and genetic factors and hyperactivation of immune cells. Patients with SLE have a high prevalence of MetS, in which elevated CVD is observed. Among the efforts of multidisciplinary healthcare teams to make an early diagnosis, a wide variety of factors have been considered and associated with the generation of biomarkers. This review aimed to elucidate some primary biomarkers and propose a set of assessments to improve the projection of the diagnosis and evolution of patients. These biomarkers include metabolic profiles, cytokines, cardiovascular tests, and microRNAs (miRs), which have been observed to be dysregulated in these patients and associated with outcomes.

Background. In obesity there is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. Chemerin is secreted in white adipose tissue and promotes low-grade inflammatory process, where it expressedCMKLR1receptor. The role of chemerin andCMKLR1in inflammatory process secondary to obesity is not defined yet.Methods. Cross-sectional study with 134 individuals classified as with and without obesity by body mass index (BMI) and IR. Body fat storage measurements and metabolic and inflammatory markers were measured by routine methods. Soluble chemerin and basal levels of insulin by ELISA and relative expression ofCMKLR1were evaluated with qPCR and2-ΔΔCTmethod.Results. Differences (P<0.05) were observed between obesity and lean individuals in body fat storage measurements and metabolic-inflammatory markers. BothCMKLR1expression and chemerin levels were increased in obesity without IR. Soluble chemerin levels correlate with adiposity and metabolic markers (r=8.8% to 38.5%),P<0.05.Conclusion. The increment ofCMKLR1expression was associated with insulin production. Increased serum levels of chemerin in obesity were observed, favoring a dysmetabolic response. The results observed in this study suggest that both chemerin andCMKLR1have opposite expression in the context of low-grade inflammatory response manifested in the development of IR.