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Updated: Jun 13, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Phosphate-induced apoptosis of hypertrophic chondrocytes is associated with a decrease in mitochondrial membrane

Susanne U Miedlich1, Alena Zalutskaya, Eric D Zhu

  • 1Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

The Journal of Biological Chemistry
|April 21, 2010
PubMed

Insights

Phosphate is crucial for regulating programmed cell death in growth plate chondrocytes, impacting mitochondrial function and bone development. This study reveals phosphate

Area of Science:

  • Skeletal Biology
  • Cellular Biology
  • Endocrinology

Background:

  • Growth plate abnormalities are linked to impaired chondrocyte apoptosis and disruptions in vitamin D action or phosphate reabsorption.
  • Low phosphate levels inhibit hypertrophic chondrocyte apoptosis, while phosphate treatment activates this process via the mitochondrial pathway.

Purpose of the Study:

  • To investigate the factors regulating hypertrophic chondrocyte apoptosis.
  • To elucidate the role of phosphate in chondrocyte apoptosis and growth plate maturation.

Main Methods:

  • Primary murine chondrocytes were cultured to assess mitochondrial membrane potential (JC-1 fluorescence) and apoptosis following phosphate treatment.
  • Erk1/2 phosphorylation was evaluated in vitro and in vivo.
  • Murine embryonic metatarsals were cultured under phosphate-restricted conditions to analyze parathyroid hormone-related protein (PTHrP) mRNA and phospho-Erk levels.

Main Results:

  • Phosphate treatment increased the percentage of cells with low mitochondrial membrane potential in hypertrophic chondrocytes.
  • Phosphate-induced apoptosis was dependent on Erk1/2 phosphorylation, confirmed by in vivo inhibition studies.
  • Phosphate restriction in cultured metatarsals led to increased PTHrP mRNA and decreased phospho-Erk in hypertrophic chondrocytes.

Conclusions:

  • Phosphate plays a key role in regulating mitochondrial membrane potential in hypertrophic chondrocytes, promoting apoptosis.
  • The Erk1/2 signaling pathway is essential for phosphate-mediated chondrocyte apoptosis and growth plate maturation.
  • The parathyroid hormone-related protein (PTHrP) signaling pathway is involved in phosphate's regulation of chondrocyte apoptosis and growth plate development.

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