Open AccessChondrocyte terminal differentiation, apoptosis, and type X collagen expression are downregulated by parathyroid hormone
Author(s) -
Harrington Erik Kern,
Lunsford Leif E.,
Svoboda Kathy K.H.
Publication year - 2004
Publication title -
the anatomical record part a: discoveries in molecular, cellular, and evolutionary biology
Language(s) - English
Resource type - Journals
eISSN - 1552-4892
pISSN - 1552-4884
DOI - 10.1002/ar.a.20129
Subject(s) - chondrocyte , parathyroid hormone , parathyroid hormone related protein , medicine , endocrinology , chondrogenesis , chemistry , type ii collagen , receptor , parathyroid hormone receptor , apoptosis , microbiology and biotechnology , messenger rna , cartilage , biology , hormone receptor , cell , calcium , biochemistry , anatomy , gene , cancer , breast cancer
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.