A self-perpetuating cycle of Type H vessel proliferation and T-2 induced inflammation drives KBD pathogenesis.
Type H vessels may be key players in the development of Kashin-Beck disease, influenced by T-2 toxin and inflammation, but further research is needed to confirm these findings in humans.
Where it sits
this study against the rest of the selank corpusSummary and findings
This study investigated the role of type H vessels in Kashin-Beck disease (KBD) using a rat model exposed to T-2 toxin and low-selenium diet. Roxadustat and Halofuginone were used to pharmacologically modulate type H vessels. The study found that Roxadustat increased type H vessel density and T-2 toxin accumulation, while Halofuginone reduced vessel proliferation and inflammation.
Abstract
<h4>Objective</h4>Kashin-Beck disease (KBD) primarily impairs the epiphyseal plate in children and adolescents, resulting in enlarged bone ends and short stature. Given the abundance of type H vessels in the growing epiphyseal plate, this spatiotemporal correlation prompted us to investigate their potential role in KBD.<h4>Methods</h4>A rat KBD model was established by feeding T-2 toxin and a low-selenium. Pharmacological modulation of type H vessels was achieved with Roxadustat (promoter) and Halofuginone (inhibitor). Rats were randomly divided into the placebo group (normal), the low-sel + T-2 group (T-2), the low-sel + T-2 + Roxadustat group (T-2 + RD) and the low-sel + T-2 + Halofuginone group (T-2 + HF). Histopathology, immunofluorescence, single-cell RNA sequencing, qPCR, and explants were employed to assess vascular density, T-2 toxin accumulation, inflammatory markers and cartilage integrity.<h4>Results</h4>Roxadustat increased type H vessel density (Mean Difference (MD): 4.11, 95%CI: 0.19, 8.04), amplified T-2 toxin accumulation near the epiphyseal plate (MD: 0.16, 95%CI: 0.062, 0.25) and exacerbated chondrocyte apoptosis and necrosis. Conversely, HF reduced type H vessel proliferation (MD: -3.70, 95%CI: -6.67, -0.73), decreased T-2 toxin levels and suppressed inflammation (MD: -0.17, 95%CI: -0.23, -0.11), while preserving proteoglycan content and cartilage morphology. Single-cell RNA sequencing, qPCR and explants revealed that T-2 toxin-induced inflammation upregulated IL-6 and SELE, promoting type H vessels proliferation.<h4>Conclusions</h4>This study identifies type H vessels as critical mediators of KBD pathogenesis, linking T-2 toxin transport, inflammation and cartilage damage. The findings highlight a vicious cycle involving type H vessel proliferation and inflammatory signaling.
Background
Kashin-Beck disease (KBD) is characterized by impaired epiphyseal plate development, leading to skeletal deformities in children. Previous research has indicated a potential link between vascular changes and KBD pathology, particularly involving type H vessels. This study aims to elucidate the role of these vessels in the disease process, particularly in the context of T-2 toxin exposure and low selenium levels.
Methods
A rat model of KBD was established using T-2 toxin and a low-selenium diet. The rats were divided into four groups: a normal placebo group, a low-selenium plus T-2 group, a low-selenium plus T-2 plus Roxadustat group, and a low-selenium plus T-2 plus Halofuginone group. Various techniques including histopathology, immunofluorescence, single-cell RNA sequencing, qPCR, and explants were employed to assess vascular density, toxin accumulation, inflammation, and cartilage integrity.
Results
Roxadustat increased type H vessel density with a Mean Difference (MD) of 4.11 (95%CI: 0.19, 8.04) and amplified T-2 toxin accumulation near the epiphyseal plate (MD: 0.16, 95%CI: 0.062, 0.25). Halofuginone resulted in a reduction of type H vessel proliferation (MD: -3.70, 95%CI: -6.67, -0.73) and decreased T-2 toxin levels (MD: -0.17, 95%CI: -0.23, -0.11).
Interpretation
The findings suggest that type H vessels play a significant role in KBD pathogenesis, particularly through their interaction with T-2 toxin and inflammatory processes. While the results are statistically significant, the clinical relevance remains uncertain due to the use of an animal model and the pharmacological approach taken. The study's design may limit the applicability of the findings to human conditions.
Key findings
- Roxadustat increased type H vessel density (Mean Difference (MD): 4.11, 95%CI: 0.19, 8.04)
- Roxadustat amplified T-2 toxin accumulation near the epiphyseal plate (MD: 0.16, 95%CI: 0.062, 0.25)
- Halofuginone reduced type H vessel proliferation (MD: -3.70, 95%CI: -6.67, -0.73)
- Halofuginone decreased T-2 toxin levels (MD: -0.17, 95%CI: -0.23, -0.11)
Limitations
- rodent model may not fully translate to humans
- pharmacological modulation may not reflect natural disease progression
- not reported in abstract