Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism

K. Mansfield, Cristina Teixeira, C. S. Adams, I. M. Shapiro

Research output: Contribution to journalArticle

Abstract

In a previous investigation we showed that phosphate ions (Pi) induced apoptosis of terminally differentiated hypertrophic chondrocytes. To explore the mechanism by which Pi induces cell death, we asked the following two questions. First, can we prevent Pi-induced apoptosis by inhibiting plasma membrane Na-Pi cotransport? Second, which specific Na-Pi transporters are expressed in chondrocytes and are they developmentally regulated? Terminally differentiated hypertrophic chondrocytes were isolated from chick tibial cartilage and cell death was measured in the presence of 3-7 mmol/L Pi. To ascertain whether apoptosis was linked to a rise in cellular Pi loading, we examined the effect of phosphonoformic acid (PFA), a competitive inhibitor of Na-Pi cotransport on Pi-induced apoptosis in chondrocytes. We found that 1 mmol/L PFA blocked anion-induced cell death and prevented an increase in the cell Pi content. In a parallel study, we determined that the bisphosphonate, alendronate, also protected chondrocytes from death, albeit at a lower concentration than PFA. Using a DNA end-labeling procedure, we showed that the Pi-treated cells were apoptotic and, as might be predicted, the presence of PFA blocked induction of the death sequence. Next, we examined the expression of two Pi transporters in relation to chondrocyte maturation and anion treatment. We noted that there was expression of the constitutive transporter, Glvr-1, and a type II cotransporter in chick growth plate cells. Although these transport systems are active in terminally differentiated cells, it is probable that the initiation of apoptosis may require the induction of other Pi-transport systems. It is concluded that, at the mineralization front, cell death is linked directly to the elevation in environmental anion concentration and the concomitant rise in intracellular Pi levels.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBone
Volume28
Issue number1
DOIs
StatePublished - 2001

Fingerprint

Membrane Transport Proteins
Chondrocytes
Phosphates
Cell Membrane
Ions
Apoptosis
Foscarnet
Ion Transport
Cell Death
Phosphate Transport Proteins
Anions
Alendronate
Growth Plate
Active Biological Transport
Diphosphonates
Cartilage

Keywords

  • Alendronate
  • Apoptosis
  • Chondrocytes
  • Glvr-1
  • Growth plate
  • Inorganic phosphate (Pi)
  • NaPi-2

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism. / Mansfield, K.; Teixeira, Cristina; Adams, C. S.; Shapiro, I. M.

In: Bone, Vol. 28, No. 1, 2001, p. 1-8.

Research output: Contribution to journalArticle

Mansfield, K. ; Teixeira, Cristina ; Adams, C. S. ; Shapiro, I. M. / Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism. In: Bone. 2001 ; Vol. 28, No. 1. pp. 1-8.
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