The Relationship Between BMP-2-induced Osteoblastic Commitment and Cell Division

The use of osteoblastic precursors for skeletal regeneration therapy still depends on the clarification of a number of fundamental events in bone cell biology. There is now convincing evidence that osteoblasts are derived from pluripotent mesenchymal stem cells (MSCs) present in the bone marrow and other connective tissue compartments that also give to chondroblasts, adipocytes and myoblasts. Bone morphogenetic proteins (BMPs) induce commitment of MSCs to the osteoblast lineage but the mechanisms involved are poorly understood. -OBJECTIVES: Based on current paradigms suggesting that stem cells originate differentiated cells via asymmetric mitoses the aims of this study were to investigate in culture 1) whether osteoblast-induced differentiation of MSCs is accompanied by cell division and 2) whether cell division is an absolute requirement for commitment. -METHODS: Quiescent C3H10T1/2 fibroblasts (an MSC cell line) were stimulated with BMP-2 in the presence or absence of the cell division-inhibitor aphidicolin and levels of osteoblast differentiation and cell division determined by cytochemical/imunocytochemical staining for alkaline phosphatase (ALP) and bromodeoxyuridine respectively. -RESULTS: BMP-2 stimulated both cell division and osteblastic commitment, but this was rarely observed within the same cell. The rate of osteoblastic commitment in cells incubated with aphidicolin were similar to controls. -CONCLUSIONS: The results of this study suggest that BMP-2-induced MSC osteoblastic commitment is not always accompanied by cell division and that cell division is not an absolute requirement for commitment.