Bone morphogenetic proteins, bone marrow stromal cells, and mesenchymal stem cells. Maureen Owen revisited.

Abstract

In postnatal mammals, there are persistent molecular signals and responding cells in bone to initiate osteogenesis and repair in response to trauma. The responding osteogenic precursor cells are of 2 categories: determined and inducible. The latter can be induced by demineralized bone matrix to form bone. Demineralized bone matrix consists of extracellular matrix and tightly associated bone morphogenetic proteins. The genes for bone morphogenetic proteins have been cloned, the recombinant proteins have been expressed, and currently their mechanism of action is being explored. Bone morphogenetic proteins are pleiotropic initiators of inducible osteogenic precursor cells. Bone morphogenetic proteins govern the 3 key steps in the osteogenic cascade: chemotaxis, mitosis, and differentiation. The receptors for bone morphogenetic proteins have been cloned and expressed and consist of 2 classes, Types I and II, that are membrane bound serine/threonine protein kinases. Bone morphogenetic proteins bind to extracellular matrix and their collaborative action on osteogenic cells culminates in the terminal differentiation of the osteoblast-osteocyte continuum. Bone morphogenetic proteins are currently on the threshold for clinical applications.