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Abstract: TH-PO522

The Effect of PKD Gene Mutation on Bone

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic


  • Gitomer, Berenice Y., Div. Renal Diseases and Hypertension,, Aurora, Colorado, United States
  • Pereira, Renata C., University of California, Los Angeles, California, United States
  • Salusky, Isidro B., Mattel Children's Hospital, Los Angeles, California, United States
  • Wang, Wei, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Hopp, Katharina, University of Colorado Denver, AMC, Aurora, Colorado, United States
  • Jovanovich, Anna Jeanette, Denver VA / University of Colorado, Denver, Colorado, United States
  • You, Zhiying, UC Denver, Aurora, Colorado, United States
  • Nowak, Kristen L., University of Colorado Denver: Anschutz Medical Campus, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado , Aurora, Colorado, United States

Kidney cysts are an invariant feature of autosomal dominant polycystic kidney disease (ADPKD). However, patients with PKD2 vs. PKD1 mutations typically have milder disease . We showed previously that ADPKD patients with normal kidney function have a low turnover bone defect. The goal of the current study was to determine whether PKD gene mutations cause differential changes on osteoblast primary cilium structure or gene expression in osteoblasts.


Primary osteoblast cultures were established from human bone obtained by iliac crest bone biopsy. In order to visualize the primary cilium, cells were serum deprived to suppress cell division and treated with LiCl. The primary cilium was stained with anti-acetylated tubulin and the base with anti-pericentrin. Cilia length was measured on 200 -300 cells from each individual. RNAseq analysis was performed on RNA extracted from trabecular bone.


Cilia on osteoblasts from ADPKD patients elongated more than those on healthy control osteoblasts in response to LiCl exposure and longer cilia were associated with PKD1 gene mutations (Figure 1). Elongation of osteoblast cilia from patients with other causes of adynamic bone disease did not differ from control cells, indicating that the gene mutation is responsible for the cilia abnormality in ADPKD. RNAseq analysis of bone from patients with PKD1 (N=12) or PKD2 (N=3) revealed decreased expression of several genes including COL1A2 and aggrecan proteoglycan (ACAN) in PKD1 compared to PKD2 bone.


PKD genotype affects both primary cilium structure and gene expression in bone from patients with ADPKD. Cilia structural abnormalities appear to be a result of the primary gene defect as they do not occur in patients with adynamic bone disease due to other causes.


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