BMP‐2, BMP‐4, and PDGF‐bb stimulate chemotactic migration of primary human mesenchymal progenitor cells

TLDR

Bone development, remodeling, and repair require recruitment of mesenchymal progenitor cells (MPCs) to differentiate into osteoblasts, a process regulated in part by growth factors released from the bone matrix. The study examined whether primary human MPCs and their differentiated osteoblast progenitors migrate toward various growth factors (rhbFGF, rhTGF‑β1, rhPDGF‑bb, rhBMP‑2, rxBMP‑4) across a range of concentrations. Chemotaxis was quantified by calculating a chemotactic index (CI) for each factor and concentration. Primary MPCs migrated dose‑dependently toward rhBMP‑2, rxBMP‑4, and rhPDGF‑bb, achieving up to 3.5‑, 3.6‑, and 22‑fold increases in CI, whereas rhTGF‑β1 and rhbFGF had no effect; differentiated progenitors showed modest 2.2‑ to 2.4‑fold responses to BMP‑2, PDGF‑bb, and TGF‑β1 but only 1.7‑ to 1.6‑fold to BMP‑4 and bFGF, indicating that BMP‑2, BMP‑4, and PDGF‑bb act as chemoattractants for MPC recruitment during bone development and fracture healing.

Abstract

For bone development, remodeling, and repair; the recruitment of mesenchymal progenitor cells (MPC) and their differentiation to osteoblasts is mandatory. The process of migration is believed to be regulated in part by growth factors stored within the bone matrix and released by bone resorption. In this study, primary human MPCs and to osteoblasts differentiated progenitor cells were examined for chemotaxis in response to human basic fibroblast growth factor (rhbFGF), human transforming growth factor beta 1 (rhTGF-beta1), human platelet derived growth factor bb (rhPDGF-bb), human bone morphogenetic protein-2 (rhBMP-2), and recombinant bone morphogenetic protein-4 of Xenopus laevis (rxBMP-4) from 0.001 to 1.0 ng/ml each. The results of migration were expressed as a chemotactic index (CI). Migration of primary human progenitor cells was stimulated by rhBMP-2, rxBMP-4, and rhPDGF-bb in a dose-dependent manner. The increase of CI was up to 3.5-fold for rhBMP-2, 3.6-fold for rxBMP-4, and up to 22-fold for rhPDGF-bb, whereas rhTGF-beta1 and rhbFGF did not stimulate cell migration in the concentration range tested. In contrast differentiated progenitor cells behave similar to primary human osteoblasts. RhBMP-2, rhPDGF-bb, and rhTGF-beta1 stimulated the migration from 2.2 to 2.4-fold each, while rxBMP-4 and rhbFGF reached only a CI of 1.7-1.6. The effect of rhBMP-2, rxBMP-4, and rhPDGF-bb as chemoattractive proteins for primary human MPC, including the change in response to growth factors after differentiation suggests a functional role for recruitment of MPCs during bone development and remodeling, as well as fracture healing.