Inositol 1,4,5-trisphosphate receptor type 2 is associated with the bone-vessel axis in chronic kidney disease-mineral bone disorder

Qiong Xiao; Yun Tang; Haojun Luo; Sipei Chen; Qiao Tang; Rong Chen; Lin Xiong; Jun Xiao; Daqing Hong; Li Wang; Guisen Li; Yi Li

doi:10.1080/0886022X.2022.2162419

Inositol 1,4,5-trisphosphate receptor type 2 is associated with the bone-vessel axis in chronic kidney disease-mineral bone disorder

Ren Fail. 2023 Dec;45(1):2162419. doi: 10.1080/0886022X.2022.2162419.

Authors

Qiong Xiao^{1

2

3

4}, Yun Tang^{1

2

3}, Haojun Luo⁵, Sipei Chen^{1

2

3}, Qiao Tang^{1

2

3}, Rong Chen^{1

2

3}, Lin Xiong^{1

2

3}, Jun Xiao⁶, Daqing Hong^{1

2

3}, Li Wang^{1

2

3}, Guisen Li^{1

2

3}, Yi Li^{1

2

3}

Affiliations

¹ Department 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.
² Sichuan Clinical Research Center for Kidney Diseases, Clinical immunology Translational Medicine Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
³ Department of Nephrology, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, Sichuan, China.
⁴ Department of Stomatology, The First Affiliated Hospital of Chongqing Medical and Pharmaceutical College, Chongqing, China.
⁵ Department of Palliative Medicine, Chongqing University Cancer Hospital, Chongqing, China.
⁶ Department of Cardiovascular Medicine, Chongqing University Center Hospital, Chongqing, China.

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.

Keywords: Bone–vessel axis; chronic kidney disease–mineral bone disorder; clinical relevance; inositol 1,4,5-trisphosphate receptor type 2; vascular calcification.

MeSH terms

Animals
Chronic Kidney Disease-Mineral and Bone Disorder* / etiology
Inositol 1,4,5-Trisphosphate Receptors* / metabolism
Kidney
Minerals / metabolism
Parathyroid Hormone
Rats

Substances

Inositol 1,4,5-Trisphosphate Receptors
Minerals
Parathyroid Hormone
ITPR2 protein, rat

Grants and funding

This work was supported by the National Natural Science Foundation of China [U21A20349, 82270729, 81700607, 8170742, 82070690, 81970641 and 81800613]; the PHD Foundation of Sichuan Academy of Sciences & Sichuan Provincial People’s Hospital [2015BS05]; the Fundamental Research Funds for the Central Universities from UESTC [ZYGX2019J105]; Key R & D projects in Sichuan Province [2019YFS0538 and 2021YFS0370]; the Department of Science and Technology of Sichuan Province [2020ZYD034 and 2021YFS0372]; the Foundation of Health and Family Planning Commission in Sichuan [16PJ424]; the Foundation of Sichuan Medical Association [S20071]; the Zhongguancun Nephrology & Blood Purification Innovation Alliance [NBPIA20QC0102] and the Discipline Construction Fund of Sichuan Provincial People’s Hospital.