Development of the terminally differentiated state sensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation

Bruna Pucci, Christopher S. Adams, Jolanta Fertala, Bradley C. Snyder, Kyle D. Mansfield, Marco Tafani, Theresa Freeman, Irving M. Shapiro

Research output: Contribution to journalArticle

Abstract

The maturation of epiphyseal chondrocytes is accompanied by dramatic changes in energy metabolism and shifts in proteins concerned with the induction of apoptosis. We evaluated the role of mitochondria in this process by evaluating the membrane potential (Δψm) of chondrocytes of embryonic tibia and the epiphyseal growth plate. We observed that there was a maturation-dependent change in fluorescence, indicating a fall in the Δψm. The level of mitochondrial Bcl-2 was decreased during maturation, while in the same time period there was an obvious increase in Bax levels in the mitochondrial fraction of the terminally differentiated chondrocytes. BclxL, another anti-apoptotic protein, was also robustly expressed in the mitochondrial fraction, but its expression was not dependent on the maturation status of the chondrocytes. We found that caspase-3 was present throughout the growth plate and in hypertrophic cells in culture. We blocked caspase-3 activity and found that alkaline phosphatase staining and mineral formation was decreased, and the cells had lost their characteristic shape. Moreover, we noted that the undifferentiated eel Is were insensitive to elevated concentrations of inorganic phosphate (Pi). It is concluded that during hypertrophy, the change in membrane potential, the increased binding of a pro-apoptotic protein to mitochondria, and the activation of caspase-3 serve to prime cells for apoptosis. Only when the terminally differentiated chondrocytes are challenged with low levels of apoptogens there is activation of apoptosis.

Original languageEnglish
Pages (from-to)609-615
Number of pages7
JournalJournal of Cellular Physiology
Volume210
Issue number3
DOIs
Publication statusPublished - Mar 2007

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Chondrocytes
Caspase 3
Apoptosis Regulatory Proteins
Mitochondria
Chemical activation
Growth Plate
Apoptosis
Membranes
Membrane Potentials
Minerals
Alkaline Phosphatase
Eels
Fluorescence
Phosphates
Tibia
Hypertrophy
Energy Metabolism
Cell Culture Techniques
Staining and Labeling
Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Pucci, B., Adams, C. S., Fertala, J., Snyder, B. C., Mansfield, K. D., Tafani, M., ... Shapiro, I. M. (2007). Development of the terminally differentiated state sensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation. Journal of Cellular Physiology, 210(3), 609-615. https://doi.org/10.1002/jcp.20857

Development of the terminally differentiated state sensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation. / Pucci, Bruna; Adams, Christopher S.; Fertala, Jolanta; Snyder, Bradley C.; Mansfield, Kyle D.; Tafani, Marco; Freeman, Theresa; Shapiro, Irving M.

In: Journal of Cellular Physiology, Vol. 210, No. 3, 03.2007, p. 609-615.

Research output: Contribution to journalArticle

Pucci, B, Adams, CS, Fertala, J, Snyder, BC, Mansfield, KD, Tafani, M, Freeman, T & Shapiro, IM 2007, 'Development of the terminally differentiated state sensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation', Journal of Cellular Physiology, vol. 210, no. 3, pp. 609-615. https://doi.org/10.1002/jcp.20857
Pucci, Bruna ; Adams, Christopher S. ; Fertala, Jolanta ; Snyder, Bradley C. ; Mansfield, Kyle D. ; Tafani, Marco ; Freeman, Theresa ; Shapiro, Irving M. / Development of the terminally differentiated state sensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation. In: Journal of Cellular Physiology. 2007 ; Vol. 210, No. 3. pp. 609-615.
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