TY - JOUR
T1 - Parathyroid hormone and transforming growth factor-β1 coregulate chondrocyte differentiation in vitro
AU - Nasatzky, E.
AU - Azran, E.
AU - Dean, D. D.
AU - Boyan, Barbara D.
AU - Schwartz, Z.
N1 - Funding Information:
We wish to acknowledge the contributions of Sandra Messier and Virginia Contreras to the preparation of the manuscript. This study was supported by USPHS grants DE-05937 and DE-08603 and by the Center for the Enhancement of the Biology/Biomaterials Interface.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Chondrocytes
KW - Differentiation
KW - Parathyroid hormone
KW - Proliferation
KW - Transforming growth factor β1
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U2 - 10.1385/ENDO:13:3:305
DO - 10.1385/ENDO:13:3:305
M3 - Article
C2 - 11216642
AN - SCOPUS:0034487031
SN - 1355-008X
VL - 13
SP - 305
EP - 313
JO - Endocrine
JF - Endocrine
IS - 3
ER -