Original Full Length ArticleSkeletal (stromal) stem cells: An update on intracellular signaling pathways controlling osteoblast differentiation

- Molecular switches of osteoblast and adipocyte are ideal “druggable” targets for enhancing bone formation.
- The non-canonical Notch signaling molecule Dlk1/Pref-1 is a novel inhibitor of bone mass.
- Wnt signaling receptor Lrp5 regulates the commitment of BMSCs into osteoblasts versus adipocytes.
- Regulating BMSC differentiation by kinase inhibitors is a novel approach for enhancing bone formation.

Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy for identifying druggable targets for enhancing bone formation. This review will discuss the functions and the molecular mechanisms of action on osteoblast differentiation and bone formation; of a number of recently identified regulatory molecules: the non-canonical Notch signaling molecule Delta-like 1/preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone.