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.

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.

The BALB/c model of pristane-induced lupus (PIL) exhibits cognitive impairment features resembling neuropsychiatric lupus (NPLSE). Osteopontin (OPN) is associated with disease activity in SLE; however, its involvement in NPLSE is not yet entirely determined. Our study aims to elucidate the contribution of full-length OPN (OPN-FL) plasma expression, OPN N-half, and Spp1 to cognitive impairment in the PIL mice model. A total of 76 female BALB/c mice were divided into pristane (P), pristane plus lipopolysaccharide (P plus LPS) and control (C) groups. In behavioral tests, the P group showed cognitive and visuospatial memory impairment. Elevated plasma OPN FL levels were found in P compared to C groups (177.7 ± 90.1 vs. 105.9 ± 56.8 ng/mL, p = 0.009) and OPN N-half was different between P and C groups (673.5 ± 144.6 vs. 624.5 ± 377.7 ng/mL, p = 0.028) and P plus LPS and C groups (624.5 ± 377.7 vs. 381.4 ± 205.0 ng/mL, p = 0.001). Anti-Sm correlated with OPN-FL (r = 0.269, p = 0.0150). The relative expression of Spp1 in the brain was 2.5 and 2.7-fold higher in P and P plus LPS groups, respectively. The evidence suggests that OPN is related to cognitive impairment in PIL mice and might play a relevant role in the detrimental neurological conditions of NPSLE.