Rat Skeletal Muscle Myoblasts are Target Cells for the Action of Native Bone Morphogenetic Protein

Abstract

Bone morphogenetic proteins (BMPs) are multifunctional proteins capable of inducing an osteogenic phenotype in various cell lines and providing alternatives to bone grafts in the field of orthopaedics. Study was carried out here of the specific binding and stimulation of markers of bone metabolism by highly purified native bovine BMP in rat skeletal myoblasts (L6). Binding studies using 125I-labeled BMP and various concentrations of unlabeled BMP showed the existence of a single-class, one-binding-site BMP receptor. The binding was time-, temperature- and dose-dependent in various experiments. In assessing the capacity of BMP to induce myoblasts to differentiate into the osteoblast lineage, osteocalcin production was initiated, alkaline phosphatase activity increased approximately four-fold and calcium uptake almost three-fold compared with control cells during four days culturing with 12.5 μg/ml of BMP. These results indicate that the L6 myoblast is a target cell for the action of native BMP, and under the influence of BMP L6 myoblasts are capable of differentiating in the direction of osteoblasts. This BMP-induced differentiation of myoblasts offers a novel assay system for in vitro detection of osteoinductivity and investigation of the mechanism of ectopic bone formation.