Chondrocyte terminal differentiation, apoptosis, and type X collagen expression are downregulated by parathyroid hormone.
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.
Harrington
Erik Kern
EK
Department of Biomedical Sciences, Texas A&M University System, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, TX 75246, USA.
Lunsford
Leif E
LE
Svoboda
Kathy K H
KK
D000818:Animals; D017209:Apoptosis; D002356:Cartilage / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D048429:Cell Size; D002645:Chickens; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024121:Collagen Type X / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007124:Immunoenzyme Techniques; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D024121:Collagen Type X; D010281:Parathyroid Hormone; D012333:RNA, Messenger