Parathyroid hormone and transforming growth factor-β1 coregulate chondrocyte differentiation in vitro

E. Nasatzky, E. Azran, D. D. Dean, Barbara D. Boyan, Z. Schwartz

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Parathyroid hormone (1-34) (PTH(1-34) and transforming growth factor-β1 (TGF-β1) regulate chondrocyte proliferation, differentiation, and matrix synthesis. Both proteins mediate their effects in a dose- and time-dependent manner, and the effects are cell maturation specific. Moreover, similar signaling pathways are used, suggesting that there may be cross talk leading to coregulated cell response. To test this hypothesis, confluent cultures of rat costochondral resting zone and growth zone chondrocytes were treated with 0.22, 0.44, or 0.88 ng/mL of rhTGF-β1 for 24 h, followed by treatment with 10 -11 to 10 -8 M PTH(1-34) for 10 min or 24 h. [ 3H]-Thymidine incorporation, specific activity of alkaline phosphatase (AP), and [ 35S]-sulfate incorporation were measured. PTH(1-34) had no effect on [ 3H]-thymidine incorporation by growth zone cells pretreated with 0.22 or 0.44 ng/mL of TGF-β1, but in cultures treated with 0.88 ng/mL, PTH(1-34) caused a dose-dependent decrease that was maximal at the lowest concentration tested. By contrast, PTH-(1-34.) stimulated [ 3H]-thymidine incorporation by resting zone cells, and this effect was additive with the stimulation caused by 0.22 ng/mL of TGF-β1. PTH(1-34) caused a synergistic increase in AP in growth zone cells treated with 0.44 or 0.88 ng/mL of TGF-β1, but not in cells treated with 0.22 ng/mL of TGF-β1. It had no effect on AP in resting zone cells pretreated with any concentration of TGF-β1. PTH(1-34) increased [ 35S]-sulfate incorporation in growth zone and resting zone cell cultures treated with 0.22 ng/mL of TGF-β1 to levels seen in cultures treated with 0.88 ng/mL of TGF-β1 alone. These results support the hypothesis that PTH(1-34) and TGF-β1 coregulate growth plate chondrocytes and that the effects are cell maturation dependent.

Original languageEnglish (US)
Pages (from-to)305-313
Number of pages9
JournalEndocrine
Volume13
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Chondrocytes
  • Differentiation
  • Parathyroid hormone
  • Proliferation
  • Transforming growth factor β1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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