Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy

Arthritis Research & Therapy

Catherine Chevalier¹  Frédéric Blanchard¹  Julien De Lima¹  Régis Brion²  Julien Herman³  Benoit Le Goff³  Christelle Darrieutort-Laffite⁴ 

[1] INSERM UMR1238, Bone Sarcoma and Remodeling of Calcified Tissues, Faculté de Médecine de Nantes, 1 rue Gaston Veil, 44035, Nantes Cedex 1, France;INSERM UMR1238, Bone Sarcoma and Remodeling of Calcified Tissues, Faculté de Médecine de Nantes, 1 rue Gaston Veil, 44035, Nantes Cedex 1, France;Nantes University Hospital, 44093, Nantes, France;INSERM UMR1238, Bone Sarcoma and Remodeling of Calcified Tissues, Faculté de Médecine de Nantes, 1 rue Gaston Veil, 44035, Nantes Cedex 1, France;Rheumatology Department, Nantes University Hospital, 44093, Nantes, France;INSERM UMR1238, Bone Sarcoma and Remodeling of Calcified Tissues, Faculté de Médecine de Nantes, 1 rue Gaston Veil, 44035, Nantes Cedex 1, France;Rheumatology Department, Nantes University Hospital, 44093, Nantes, France;Current Address: McKay Orthopedic Research Laboratory, University of Pennsylvania, 307A Stemmler Hall, 3450 Hamilton Walk, 19104-6081, Philadelphia, PA, USA;

关键词: Apatite;    Rotator cuff tendons;    Interleukin-1;    Inflammasome;    Air pouch model;   

DOI  :  10.1186/s13075-021-02516-9

来源: Springer

【 摘 要 】

BackgroundCalcific 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.MethodsHuman 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.ResultsHuman 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.ConclusionsAs 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.

【 授权许可】

CC BY