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Kidney Week

Abstract: PO0329

Vitamin D Deficiency, Investigating the Connection Between Osteoporosis and CKD

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Dona, Reanna A., Albert Einstein College of Medicine, Bronx, New York, United States
  • Greally, John M., Albert Einstein College of Medicine, Bronx, New York, United States
Background

Chronic kidney disease (CKD) is estimated to afflict thirty-seven million people in the United States and leads to drastic alteration in bone and calcium metabolism. Metabolic bone disease is a common complication, resulting in skeletal consequences and CKD-associated osteoporosis. This occurs due to a combination of abnormalities in calcium, phosphorus, parathyroid hormone, vitamin D metabolism, and dysregulation in both bone formation, and bone resorption. One mechanism of the pathophysiology of age-associated osteoporosis is the shift in lineage commitment of mesenchymal stem cells (MSCs) towards adipogenesis at the expense of osteogenesis. Recent studies have implicated MSCs as mediators of osteoporosis due to the disrupted endocrine signaling pathways in aging individuals, similar to individuals with CKD.

Methods

We performed a re-analysis of a published single cell transcriptomics dataset investigating differentiation of MSCs to osteoblasts and adipocytes. We employed a standard pipeline from the R package “Seurat” to examine transcriptional heterogeneity of undifferentiated mesenchymal stem cells. Additionally, we tested the effects of 1,25D on MSC differentiation towards the osteogenic lineage.

Results

Here, we demonstrate heterogeneity of bone-marrow derived MSCs at the transcriptional level, implying potential underlying functional heterogeneity. Using single cell transcriptomics, we characterize the subpopulations of MSCs, multipotent stem cells and cells poised for differentiation. Once we confirmed this heterogeneity, we investigated stem cell priming with the vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25D), testing the memory of a prior exposure to stem cells influences later lineage commitment choices. Vitamin D supplementation is a common therapeutic intervention for osteoporosis and is especially key for patients with CKD-associated osteoporosis as Vitamin D deficiency is prevalent in populations at-risk for developing osteoporosis and patients already diagnosed with CKD.

Conclusion

This project supports the commonly used treatment for development and prevention of osteoporosis and demonstrates functional heterogeneity of MSCs. Further steps in this project will explore the response to vitamin D priming at a higher resolution by employing single cell RNA-sequencing.

Funding

  • Other NIH Support