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Inositol 1,4,5-trisphosphate receptor type 2 is associated with the bone-vessel axis in chronic kidney
Qiong Xiao1,2,3,4, Yun Tang1,2,3, Haojun Luo5
1Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Insights
In chronic kidney disease-mineral bone disorder (CKD-MBD), the bone-vessel axis is disrupted. Researchers identified inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) as a potential therapeutic target for this condition.
Area of Science:
- Nephrology
- Endocrinology
- Vascular Biology
- Bone Metabolism
Background:
- Chronic kidney disease-mineral bone disorder (CKD-MBD) is linked to impaired bone and cardiovascular health.
- The precise mechanisms governing the bone-vessel axis in CKD-MBD remain incompletely understood.
- Disruption of the bone-vessel axis contributes to renal osteopathy and cardiovascular complications.
Purpose of the Study:
- To investigate the pathophysiological characteristics of the bone-vessel axis in a rat model of CKD-MBD.
- To identify novel molecular targets within the aorta associated with the bone-vessel axis in CKD-MBD.
- To explore the role of inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) in CKD-MBD.
Main Methods:
- Establishment of a CKD-MBD rat model.
- Assessment of bone microarchitecture and serum bone metabolic parameters.
- RNA sequencing of aortic tissue to identify differentially expressed genes.
- Analysis of ITPR2 expression in rat aortic smooth muscle cells and serum levels in rats and patients.
Main Results:
- CKD-MBD rats exhibited deteriorated femoral trabecular bone microarchitecture and aggravated alveolar bone loss.
- RNA sequencing revealed a significant decrease in aortic inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene expression in CKD-MBD rats.
- Serum ITPR2 levels were elevated in patients with vascular calcification and showed correlations with kidney function and bone turnover markers.
Conclusions:
- The study highlights the disordered bone-vessel axis in CKD-MBD.
- ITPR2 emerges as a potential key player in the bone-vessel axis dysfunction associated with CKD-MBD.
- ITPR2 may represent a novel therapeutic target for managing vascular complications in CKD-MBD.
Abstract:
Objective: The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone-vessel axis in chronic kidney disease-mineral bone disorder (CKD-MBD). However, the mechanism of the bone-vessel axis in CKD-MBD remains unclear.Methods: We established a CKD-MBD rat model to observe the pathophysiological phenotype of the bone-vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone-vessel axis in CKD-MBD.Results: The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD-MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD-MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD-MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD-MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD-MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels.Conclusion: These findings provide preliminary insights into the role of ITPR2 in the bone-vessel axis in CKD-MBD. Thus, ITPR2 may be a potential target of the bone-vessel axis in CKD-MBD.
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