Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy
| العنوان: | Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy |
|---|---|
| المؤلفون: | Catherine Chevalier, Julien Herman, Frédéric Blanchard, Julien De Lima, Christelle Darrieutort-Laffite, Benoit Le Goff, Régis Brion |
| المصدر: | Arthritis Research & Therapy, Vol 23, Iss 1, Pp 1-11 (2021) Arthritis Research & Therapy |
| بيانات النشر: | Research Square Platform LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Rotator cuff tendons, Pathology, medicine.medical_specialty, Myeloid, Inflammasomes, Interleukin-1beta, Inflammation, Diseases of the musculoskeletal system, Inflammasome, 03 medical and health sciences, 0302 clinical medicine, In vivo, Apatites, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Humans, Apatite, 030203 arthritis & rheumatology, Chemistry, Caspase 1, Air pouch model, Interleukin, medicine.disease, In vitro, 030104 developmental biology, medicine.anatomical_structure, RC925-935, Tendinopathy, Tumor necrosis factor alpha, medicine.symptom, Research Article, Interleukin-1, medicine.drug, Calcification |
| الوصف: | Background Calcific tendonitis of the rotator cuff is due to carbonated apatite deposits in the shoulder tendons. During the evolution of the disease, an acute inflammatory episode may occur leading to the disappearance of the calcification. Although hydroxyapatite crystal-induced inflammation has been previously studied with synthetic crystals, no data are available with calcifications extracted from patients suffering from calcific tendinopathy. The objective of the study was to explore the inflammatory properties of human calcifications and the pathways involved. Methods Human calcifications and synthetic hydroxyapatite were used in vitro to stimulate human monocytes and macrophages, the human myeloid cell line THP-1, and human tenocytes. The release of IL-1β, IL-6, and IL-8 by cells was quantified by ELISA. The gene expression of pro- and anti-inflammatory cytokines was evaluated by quantitative PCR. NF-kB activation and NLRP3 involvement were assessed in THP-1 cells using a NF-kB inhibitor and a caspase-1 inhibitor. The inflammatory properties were then assessed in vivo using a mouse air pouch model. Results Human calcifications were able to induce a significant release of IL-1β when incubated with monocytes, macrophages, and THP-1 only if they were first primed with LPS (monocytes and macrophages) or PMA (THP-1). Stimulation of THP-1 by human calcifications led to similar levels of IL-1β when compared to synthetic hydroxyapatite although these levels were significantly inferior in monocytes and macrophages. The patient’s crystals enhanced mRNA expression of pro-IL-1β, as well as IL-18, NF-kB, and TGFβ when IL-6 and TNFα expression were not. IL-1β production was reduced by the inhibition of caspase-1 indicating the role of NLRP3 inflammasome. In vivo, injection of human calcifications or synthetic hydroxyapatite in the air pouch led to a significant increase in membrane thickness although significant overexpression of IL-1β was only observed for synthetic hydroxyapatite. Conclusions As synthetic hydroxyapatite, human calcifications were able to induce an inflammatory response resulting in the production of IL-1β after NF-kB activation and through NLRP3 inflammasome. In some experiments, IL-1β induction was lower with human calcifications compared to synthetic apatite. Differences in size, shape, and protein content may explain this observation. |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a18bc9d94eb8b9d074ab6b6da7d601edTest https://doi.org/10.21203/rs.3.rs-156807/v1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a18bc9d94eb8b9d074ab6b6da7d601ed |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |