Uremic Serum Impairs Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stromal Cells

J Cell Physiol. 2017 Aug;232(8):2201-2209. doi: 10.1002/jcp.25732. Epub 2017 Mar 1.

Abstract

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is characterized by an increased fracture risk. Bone marrow mesenchymal stromal cells (BMSCs) may be involved in the pathogenesis of bone disease and, in view of their promising potential applications in bone tissue engineering, the effect of uremia on BMSCs regenerative potential represents a central issue. The present study evaluated in vitro the effect of a serum pool from hemodialysis patients on BMSCs to observe its influence on osteogenic differentiation. Besides alterations in spatial organization and cytotoxicity along with hyperproliferation, gene expression analysis suggested an impairment in the osteogenic differentiation. More importantly, Receptor activator of nuclear factor kappa-B ligand (RANKL) was upregulated with a mild reduction in osteoprotegerin levels. In summary, uremic environment seems to impair BMSCs osteogenic differentiation. Moreover BMSCs themselves may enhance osteoclastogenesis, feasibly contributing to the altered bone remodeling in CKD-MBD patients. J. Cell. Physiol. 232: 2201-2209, 2017. © 2016 Wiley Periodicals, Inc.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / metabolism
  • Apoptosis
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Cell Cycle Checkpoints
  • Cell Differentiation*
  • Cell Lineage
  • Cell Proliferation
  • Cell Shape
  • Cell Survival
  • Cells, Cultured
  • Cellular Microenvironment
  • Female
  • Gene Expression Regulation
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / therapy
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Middle Aged
  • Osteogenesis*
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism
  • Phenotype
  • RANK Ligand / genetics
  • RANK Ligand / metabolism
  • Renal Dialysis
  • Time Factors
  • Uremia / blood*
  • Uremia / genetics
  • Uremia / pathology
  • Uremia / therapy

Substances

  • Osteoprotegerin
  • RANK Ligand
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Alkaline Phosphatase