Stimulation of Osteoblast Proliferation by C‐Terminal Fragments of Parathyroid Hormone–Related Protein

Parathyroid hormone (PTH)‐related protein (107–139) (PTHrP(107–139)) and PTHrP(107–111) have been reported to be potent inhibitors of isolated osteoclast activity, and inhibition of bone resorption by PTHrP(107–139) occurs in vivo. However, the actions of C‐terminal PTHrP on osteoblast activity has not been studied much. The present study addresses this issue by examining the effect of PTHrP(107–139), PTHrP(107–119), PTHrP(120–139), and PTHrP(107–111) on the proliferation of fetal rat osteoblasts. Treatment with PTHrP(107–139) for 24 h caused a dose‐dependent increase in cell number, [3H]thymidine and [3H]phenylalanine incorporation in cultured osteoblasts. The effect was apparent at concentrations of 10−10 M and greater and was sustained over time. PTHrP(107–119) and PTHrP(107–111) had effects on cell number, DNA, and protein synthesis which were comparable to those of PTHrP(107–139), whereas PTHrP(120–139) was without effect. Retroverted PTHrP(107–111) also stimulated all three activities but was only one tenth as potent as PTHrP(107–139). PTHrP(107–139) had no effect on osteoblast apoptosis. It is concluded that PTHrP(107–139) is not only an inhibitor of osteoclastic bone resorption but that it also stimulates osteoblast growth. This activity resides within the pentapeptide fragment PTHrP(107–111). These findings support a possible role for C‐terminal fragments of PTHrP in the normal regulation of bone cell function and, possibly, bone mass.