Chondrocyte terminal differentiation, apoptosis, and type X collagen expression are downregulated by parathyroid hormone

Authors

  • Erik Kern Harrington,

    1. Biomedical Sciences, Texas A&M University System, Baylor College of Dentistry, Dallas, Texas
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  • Leif E. Lunsford,

    1. Emergency Medicine, University of Southern California, San Diego, California
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  • Kathy K.H. Svoboda

    Corresponding author
    1. Biomedical Sciences, Texas A&M University System, Baylor College of Dentistry, Dallas, Texas
    2. Department of Ophthalmology, Southwestern Medical Center, Dallas, Texas
    • Department of Biomedical Science, Texas A&M Health Science Center, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246
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    • Fax: 214-828-8951


Abstract

Parathyroid hormone (PTH) regulates calcium and phosphate homeostasis through the endocrine system. Parathyroid hormone-related peptide (PTHrP) is a heterogeneous polypeptide with sequence homology to PTH in its first 13 amino acid residues. Both bind and activate a common receptor, the type 1 PTH/PTHrP receptor (PTH1R). Activation of this G-protein-coupled receptor by PTHrP has been shown to regulate chondrogenesis in a manner that attenuates chondrocyte hypertrophy. Here, we report the dose-response (10−7 to 10−15 M) effects of PTH on chondrogenesis using an avian sternal organ culture model. PTH increased cartilaginous tissue length and downregulated the deposition of type X collagen and its mRNA expression. In addition, PTH increased chondrocyte cell diameter in prehypertrophic and proliferative regions while decreasing chondrocyte apoptosis in the hypertrophic zone. In conclusion, these experiments demonstrate that PTH regulates cartilage growth, chondrocytic apoptosis, deposition of type X collagen protein, and expression of type X collagen mRNA. Type X collagen mRNA expression was downregulated by PTH in this organ culture model, but cell size, another marker for terminal differentiation, increased. © 2004 Wiley-Liss, Inc.

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