Osteoarthritis is a high-incidence painful and debilitating disease characterized by progressive degeneration of articular joints, which indicates a breakdown in joint homeostasis favoring catabolic processes. Biomechanical loading, associated with inflammatory and metabolic imbalances of joint, strongly contributes to the initiation and progression of the disease. Obesity is a primary risk factor for disease onset, and mechanical factors increased the risk for disease progression. Moreover, inflammatory mediators, in particular, adipose tissue-derived cytokines (better known as adipokines) play a critical role linking obesity and osteoarthritis. The present article summarizes the knowledge about the role of adipokines in cartilage and bone function, highlighting their contribution to the imbalance of joint homeostasis and, consequently, pathogenesis of osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:594-604, 2018.

In the intestine, interaction between epithelial cells and macrophages (MΦs) create a unique immunoregulatory microenvironment necessary to maintain local immune and tissue homeostasis. Human intestinal epithelial cells (IECs) have been shown to express interleukin (IL)-10, which keeps epithelial integrity. We have demonstrated that bacterial signaling through Toll-like receptor (TLR) 4 induces 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) synthesis in intestinal MΦs by cyclooxygenase (Cox)-2 expression. Here, we show that TLR4 signaling generates crosstalk between IECs and MΦs that enhances IL-10 expression in IECs. Direct stimulation of TLR4 leads to the expression of IL-10 in IECs, while the presence of MΦs in a Transwell system induces another peak in IL-10 expression in IECs at a later time point. The second peak of the IL-10 expression is two times greater than the first peak. This late induction of IL-10 depends on the nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ that is accumulated in IECs by TLR4-mediated inhibition of the ubiquitin-proteasomal pathway. TLR4 signaling in MΦs in turn synthesizes 15d-PGJ2 through p38 and ERK activation and Cox-2 induction, which activates PPARγ in IECs. These results suggest that TLR4 signaling maintains IL-10 production in IECs by generating epithelial-MΦs crosstalk, which is an important mechanism in the maintenance of intestinal homeostasis mediated through host-bacterial interactions.

We studied the distribution of the HLA-DRB1, -DQA1 and -DQB1 alleles in 44 Afro-Brazilian patients with multiple sclerosis and 88 controls. Although no significant differences were found between the patients and controls for the DRB1 and DQA1 alleles, the HLA-DQB1*0602 allele was positively associated with multiple sclerosis (45.0% vs. 17.0%, Pc=0.024, RR=3.31). The positive extended haplotypes for DQB1*0602 were more frequent in patients than controls, although the differences were not statistically significant in any of them. These results in Afro-Brazilians are in line with other studies which have found DQB1*0602 to be associated with the disease in the absence of the DRB1*1501 allele. We therefore think that the association with the disease in this ethnic group is more allelic than haplotypic.

BackgroundThe Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire, a 31-item, multidimensional, self-administrated questionnaire that is available in 14 languages including Spanish, has been validated using a large international sample. We investigated the validity and reliability of the Spanish version of MusiQoL in Spain.MethodsConsecutive patients with different types and severities of multiple sclerosis (MS) were recruited from 22 centres across Spain. All patients completed the MusiQoL questionnaire, the 36-Item Short Form (SF-36) health survey, and a symptoms checklist at baseline and 21 days later. External validity, internal consistency, reliability and reproducibility were tested.ResultsA total of 224 Spanish patients were evaluated. Dimensions of MusiQoL generally demonstrated a high internal consistency (Cronbach's alpha: 0.70-0.92 for all but two MusiQoL domain scores). External validity testing revealed that the MusiQoL index score correlated significantly with all SF-36 dimension scores (Pearson's correlation: 0.46-0.76), reproducibility was satisfactory (intraclass correlation coefficient: 0.60-0.91), acceptability was high, and the time taken to complete the 31-item questionnaire was reasonable (mean [standard deviation]: 9.8 [11.8] minutes).ConclusionsThe Spanish version of the MusiQoL questionnaire appears to be a valid and reliable instrument for measuring quality of life in patients with MS in Spain and constitutes a useful instrument to measure health-related quality of life in the clinical setting.