Effects of parathyroid hormone on porcine mesenchymal stem cell differentiation

Abstract

Parathyroid hormone (PTH) effects on mesenchymal stem cell (MSC) differentiation are dependent on the timing of treatment and culture conditions. In this study, we have characterized the effects of either continuous (CONT) or intermittent (2h/day, INT) PTH treatment on porcine MSC (pMSC) differentiation in media designed to promote proliferation. After 6d of culture, proliferation and gene expression were analyzed and alkaline phosphatase (ALP) activity was determined. The expression of Runx2, ALP, PPARG, LPL and PTHR were increased (P < 0.05) with either PTH treatment. Either PTH treatment also significantly increased (P < 0.05) the percentage of ALP+ cells (10% and 25% for CONT and INT compared to the control, respectively), and decreased (P < 0.05) cell proliferation (20 and 25% compared to the control for CONT and INT, respectively). We have previously shown that 1,25(OH)2D3 stimulates adipocytic differentiation of pMSC and wanted to examine the interaction of PTH with 1,25(OH)2D3 treatment. The ability of PTH to stimulate osteoblastic differentiation was completely inhibited by co‐treatment with 1,25(OH)2D3 as seen by decreased (P < 0.05) ALP+ cells and reduced (P < 0.05) expression of Runx2, ALP and PTHR by greater than 2 fold. These data suggest that PTH stimulates differentiation of pMSC. Also, 1,25(OH)2D3 inhibits the ability of PTH to stimulate MSC toward osteoblast differentiation.