Cascão, R., Vidal, B., Jalmari Finnilä, M. A., Lopes, I. P., Teixeira, R. L., Saarakkala, S., … Fonseca, J. E. (2017). Effect of celastrol on bone structure and mechanics in arthritic rats. RMD Open, 3(2), e000438. https://doi.org/10.1136/rmdopen-2017-000438
Effect of celastrol on bone structure and mechanics in arthritic rats
|Author:||Cascão, Rita1; Vidal, Bruno1; Finnilä, Mikko Arttu Jalmari2,3;|
1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
2Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
3Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
4Department of Rheumatology, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon Academic Medical Centre, Lisbon, Portugal
5Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
6Instituto Gulbenkian de Ciência, Oeiras, Portugal
|Online Access:||PDF Full Text (PDF, 1.9 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019112243848
|Publish Date:|| 2019-11-22
Objective: Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the effect of celastrol in local and systemic bone loss.
Methods: Celastrol was administrated intraperitoneally at a dose of 1 µg/g/day to female Wistar adjuvant-induced arthritic rats. Rats were sacrificed after 22 days of disease progression, and blood, femurs, tibiae and paw samples were collected for bone remodelling markers quantification, 3-point bending test, micro-CT analysis, nanoindentation and Fourier transform infrared spectroscopy measurements, and immunohistochemical evaluation.
Results: We have observed that celastrol preserved articular structures and decreased the number of osteoclasts and osteoblasts present in arthritic joints. Moreover, celastrol reduced tartrate-resistant acid phosphatase 5b, procollagen type 1 amino-terminal propeptide and C terminal crosslinked telopeptide of type II collagen serum levels. Importantly, celastrol prevented bone loss and bone microarchitecture degradation. Celastrol also preserved bone nanoproperties and mineral content. Additionally, animals treated with celastrol had less fragile bones, as depicted by an increase in maximum load and yield displacement.
Conclusions: These results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3126 Surgery, anesthesiology, intensive care, radiology
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.