Effect of celastrol on bone structure and mechanics in arthritic rats

Abstract

ObjectiveRheumatoid 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.MethodsCelastrol 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.ResultsWe 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.ConclusionsThese results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.

Resveratrol and Celastrol Loaded Collagen Dental Implants Regulate Periodontal Ligament Fibroblast Growth and Osteoclastogenesis of Bone Marrow Macrophages

“…In contrast, the addition of Cel had not contributed any significant changes in HPLF proliferation. Previously, Cascão et al . reported that intraperitoneal administration of Cel to female Wistar adjuvant‐induced arthritic rats decreased the osteoblasts number in arthritic joints.…”

“…Earlier in vitro and in vivo studies revealed that Res treatment significantly reduced bone loss due to trauma by reducing osteoclastogenic regulatory genes in periodontal ligament tissue and the differentiation of osteoclastogenic precursors (BMM and RAW 264.7 cells) . Intraperitoneal administration of Cel reduced both bone resorption and cartilage degradation in female Wistar adjuvant‐induced arthritic rats …”

Celastrol Efficacy by Oral Administration in the Adjuvant-Induced Arthritis Model

“…Normality distribution was assessed by D'Agostino and Pearson test. The treated groups (celastrol 1, 2.5, 5, and 7.5 ug/g) were compared against the untreated arthritic group with the Mann-Whitney test with Bonferroni correction to account for multiple comparisons, as previously reported (17). Thus, applying the Bonferroni correction, we divided the global significance level at 0.05 by the number of independent tests (n = 4) to get the Bonferroni critical value of p < 0.0125, below which a test would be significant.…”

A microfluidic chip-based co-culture of fibroblast-like synoviocytes with osteoblasts and osteoclasts to test bone erosion and drug evaluation

“…Celastrol was also reported to attenuate bone erosion in collagen-induced arthritis mice and inhibits osteoclast differentiation and function in RANKL-induced RAW264.7 [ 39 ]. In the microfluidic device, celastrol inhibited SW982 migration and simultaneously suppressed TRAP activity in RAW264.7 cells, suggesting a cellular mechanism of celastrol by which celastrol exerted an effective treatment in RA rats through preventing bone loss and bone microarchitecture degradation [ 40 ]. We also found that celastrol did not enhance ALP activity of BMSC.…”