PMID- 33723731 OWN - NLM STAT- MEDLINE DCOM- 20210721 LR - 20210721 IS - 1434-9949 (Electronic) IS - 0770-3198 (Linking) VI - 40 IP - 8 DP - 2021 Aug TI - Soluble inflammatory mediators of synoviocytes stimulated by monosodium urate crystals induce the production of oxidative stress, pain, and inflammation mediators in chondrocytes : Secretome of synoviocytes induces chondrocyte damage. PG - 3265-3271 LID - 10.1007/s10067-021-05676-w [doi] AB - We hypothesized that the secretion of inflammatory mediators from synoviocytes affects the chondrocyte homeostasis of articular cartilage. This study was a preliminary attempt to elucidate the molecular mechanisms by which soluble mediators obtained from activated synoviocytes induce oxidative stress and inflammation in chondrocytes. We measured the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), superoxide anion (O(2)(*-)), hydrogen peroxide (H(2)O(2)), and nitric oxide (NO(*)) from articular human cells. First, we created a conditional basal medium by exposing synoviocytes (HS) to monosodium urate crystals (CBM). The chondrocytes were exposed to either CBM (CCM), urate crystals directly (CMSU), or remained untreated (CC) as a negative control. Data were analyzed by ANOVA tests; Bonferroni test was performed for multiple comparisons between groups. Interestingly, we observed that mediators of inflammation and oxidative stress were significantly higher in CCM than CMSU and CC groups (P<0.01). The specific concentrations were as follows: 19.85 ng/mL of IL-6, 9.79 ng/mL of IL-8, 5.17 ng/mL of NGF, and 11.91 ng/mL of MCP-1. Of note, we observed the same trend for reactive oxygen and nitrogen species (P<0.001). Soluble mediators secreted by synoviocytes after being activated with MSU crystals (as observed in individuals who present gout attacks) trigger chondrocyte activation intensifying the articular inflammatory, oxidative, and pain states that damage cartilage in OA; this damage is more severe even when compared to HC directly exposed to monosodium urate crystals. Key Points * The molecular relation between MSU depositions and cartilage damage could be mediated by pro-inflammatory soluble mediators and oxidative molecules. * The secretion of pro-inflammatory mediators by activated synoviocytes is more harmful to chondrocytes than a direct activation in the chondrocyte culture. * Under this model, there is an important imbalance in the matrix homeostasis due to changes in several chemokines, cytokines, and other factors such as NGF, as well as oxidative mediators. CI - (c) 2021. International League of Associations for Rheumatology (ILAR). FAU - Lopez-Reyes, Alberto AU - Lopez-Reyes A AD - Gerosciences Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, C.P.14389, Tlalpan, Mexico City, Mexico. allorey@yahoo.com. AD - School of Health Sciences, Anahuac Mexico University, South Campus, Mexico City, Mexico. allorey@yahoo.com. FAU - Medina-Luna, Daniel AU - Medina-Luna D AD - Gerosciences Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, C.P.14389, Tlalpan, Mexico City, Mexico. AD - Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada. FAU - Santamaria-Olmedo, Monica AU - Santamaria-Olmedo M AD - Gerosciences Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, C.P.14389, Tlalpan, Mexico City, Mexico. AD - Synovial Fluid Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, Tlalpan, Mexico City, Mexico. FAU - Martinez-Flores, Karina AU - Martinez-Flores K AD - Synovial Fluid Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, Tlalpan, Mexico City, Mexico. FAU - Zamudio-Cuevas, Yessica AU - Zamudio-Cuevas Y AD - Synovial Fluid Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, Tlalpan, Mexico City, Mexico. FAU - Fernandez-Torres, Javier AU - Fernandez-Torres J AD - Synovial Fluid Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, Tlalpan, Mexico City, Mexico. FAU - Martinez-Nava, Gabriela Angelica AU - Martinez-Nava GA AD - Gerosciences Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, C.P.14389, Tlalpan, Mexico City, Mexico. AD - Synovial Fluid Laboratory, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, Tlalpan, Mexico City, Mexico. FAU - Olivos-Meza, Anell AU - Olivos-Meza A AD - Arthroscopy Service, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Ministry of Public Health, Calzada Mexico-Xochimilco 289, Tlalpan, Mexico City, Mexico. FAU - Camacho-Rea, Carmen AU - Camacho-Rea C AD - Department of Animal Nutrition, National Institute of Medical Sciences and Nutrition Salvador Zubiran (INCMNSZ), Vasco de Quiroga, No.15, Tlalpan, Mexico City, Mexico. FAU - Fernandez-Moreno, Mercedes AU - Fernandez-Moreno M AD - Rheumatology Service, Research Department, INIBIC, CIBER-BBN, A Coruna, Spain. FAU - Blanco, Francisco J AU - Blanco FJ AD - Rheumatology Service, Research Department, INIBIC, CIBER-BBN, A Coruna, Spain. FAU - Pineda, Carlos AU - Pineda C AD - Department of Rheumatic and Musculoskeletal Diseases, National Institute of Rehabilitation Luis Guillermo Ibarra-Ibarra, Mexico City, Mexico. LA - eng PT - Journal Article DEP - 20210316 PL - Germany TA - Clin Rheumatol JT - Clinical rheumatology JID - 8211469 RN - 0 (Inflammation Mediators) RN - 268B43MJ25 (Uric Acid) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Cells, Cultured MH - *Chondrocytes MH - Humans MH - Hydrogen Peroxide MH - Inflammation Mediators MH - Oxidative Stress MH - Pain MH - *Synoviocytes MH - Uric Acid OTO - NOTNLM OT - Gout OT - Osteoarthritis OT - Oxidative mediators OT - Pro-inflammatory Interleukins OT - Secretome-activated synoviocytes EDAT- 2021/03/17 06:00 MHDA- 2021/07/22 06:00 CRDT- 2021/03/16 07:01 PHST- 2020/12/14 00:00 [received] PHST- 2021/03/01 00:00 [accepted] PHST- 2021/02/24 00:00 [revised] PHST- 2021/03/17 06:00 [pubmed] PHST- 2021/07/22 06:00 [medline] PHST- 2021/03/16 07:01 [entrez] AID - 10.1007/s10067-021-05676-w [pii] AID - 10.1007/s10067-021-05676-w [doi] PST - ppublish SO - Clin Rheumatol. 2021 Aug;40(8):3265-3271. doi: 10.1007/s10067-021-05676-w. Epub 2021 Mar 16.