Abstract: SA-PO900

Bone Expression of HIF-1 in Osteocytes Is Decreased in CKD Rats

Session Information

  • Mineral Disease: CKD-Bone
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

  • 1203 Mineral Disease: CKD-Bone

Authors

  • Bisson, Sarah-Kim, CHU de Québec, Université Laval, HDQ, Québec, Quebec, Canada
  • Ung, Roth-Visal, CHU de Québec, Université Laval, HDQ, Québec, Quebec, Canada
  • Picard, Sylvain, CHU de Québec, Université Laval, HDQ, Québec, Quebec, Canada
  • Richard, Darren E, Université Laval, Québec, Quebec, Canada
  • Agharazii, Mohsen, CHU de Québec, Université Laval, HDQ, Québec, Quebec, Canada
  • Lariviere, Richard, CHU de Québec, Université Laval, HDQ, Québec, Quebec, Canada
  • Mac-Way, Fabrice, CHU de Québec, Université Laval, HDQ, Québec, Quebec, Canada
Background

Different studies, including our own, have shown that hypoxia-inducible factor-1 (HIF-1) enhances vascular calcification. However, HIF-1’s role in chronic kidney disease (CKD)-related bone disease is currently unknown. The aim of this study is to determine bone HIF-1 expression in chronic kidney disease (CKD) rats with vascular calcification.

Methods

CKD was induced by 5/6 nephrectomy and vascular calcification by a supplement of calcium, phosphorus and 1,25-dihydroxyvitamin D3 (Ca/P/VitD). Three groups were studied: control (n=8), CKD (n=14) and CKD + Ca/P/VitD (n=12). At 2 months, tibia bone and thoracic aorta were harvested for micro-CT, histomorphometry and vascular calcification quantification. HIF-1α expression, the essential HIF-1 subunit, was assessed in the tibia by immunohistochemistry and quantified using ImageJ.

Results

Vascular calcification occurred only in CKD + Ca/P/VitD rats. Compared to controls, CKD and CKD + Ca/P/VitD rats presented with a lower bone volume and bone mineral content, while trabecular thickness and separation were significantly increased in the CKD+Ca/P/vitD group. Osteoid volume and surface were also increased in CKD + Ca/P/VitD rats, which is compatible with a mineralisation defect (low turnover and mineralisation parameters). HIF-1α was expressed in osteocytes. Interestingly, the proportion of positive osteocytes for HIF-1α was decreased in CKD and CKD+Ca/P/vitD rats as compared to the controls (respectively 63.01 ± 16.78% vs 60.91 ± 23.17% vs 89.31 ± 5.87% in controls, p<0.01)

Conclusion

Our study is the first to describe HIF-1 expression in bone from CKD rats with vascular calcification. Since HIF-1 was previously suggested to play a role in bone formation, these results suggest that lower osteocyte HIF-1 expression could be involved in the development of bone anomalies during CKD.

Funding

  • Government Support - Non-U.S.