Amino-terminal Fragment (1-34) of Parathyroid Hormone-related Protein Inhibits Migration and Proliferation of Cultured Vascular Smooth Muscle Cells

We investigated the effects of amino-terminal fragment (1-34) of parathyroid hormone-related protein [PTHrP-(1-34)] on the migration and proliferation of vascular smooth muscle cells (VSMCs). Cultured VSMCs (5-9th passage) obtained from the aortas of male Wistar rats were used in this study. Migration of VSMCs was assessed using a modified Boyden's chamber. Proliferation of VSMCs was evaluated by measuring [3H]thymidine incorporation and counting cell numbers. PTHrP-(1-34) inhibited 10% fetal bovine serum (FBS)-induced increase in migration of VSMCs (61% of control at 1 micromol/l) in a concentration-dependent manner. PTHrP-(1-34) also inhibited 5% FBS-induced increase in [3H]thymidine incorporation (37% of control at 1 micromol/l) and cell number of VSMCs (33% of control at 1 micromol/l) in a concentration-dependent manner. Parathyroid hormone (PTH)-(1-34) inhibited the migration and DNA synthesis of VSMCs to a similar extent. PTHrP-(7-34), a PTH/PTHrP receptor antagonist, significantly inhibited these effects of PTHrP and PTH. PTHrP-(1-34) also inhibited platelet-derived growth factor-BB (5 ng/ml)-induced migration and DNA synthesis of VSMCs. These findings suggest that PTHrP-(1-34) inhibits the migration and proliferation of VSMCs through PTH/PTHrP receptors.