Molecular mechanisms of skeletal tissue formation

Abstract

Vertebrate skeleton consists of numerous pieces of bone and cartilage, each placed at the appropriate anatomical site by an elaborate regulatory process in developmental patterning. In this process, mesenchymal cells initially form aggregates at the respective anatomical sites. These aggregates later generate chondrocytes that form a cartilage anlagen and further differentiate into hypertrophic chondrocytes in the growth plate cartilage that is replaced by bone through endochondral bone formation. In an alternative pathway, skeletogenic mesenchymal progenitor cells directly generate osteoblasts through an intramembranous bone formation process. In recent decades, considerable studies have been performed to understand the molecular mechanisms of these processes. By reviewing recent studies, the author attempts to address how the critical transcription factors and secreted factors regulate skeletal tissue formation. Emphasis is placed mainly on the in vivo functions of transcription factors Sox9, Runx2, and Osterix, and signaling exerted by secreted molecules such as Bone morphogenetic proteins (BMPs), Transforming growth factor β (TGF-β), Wnts, Fibroblast growth factors (FGFs), Indian hedgehog (Ihh), and Parathyroid hormone-related protein (PTHrP). Each of these factors is essential for the proper progression of skeletal tissue formation. Elucidation of the mechanisms that govern differentiation of skeletal cells would further contribute to our understanding of maintenance and diseases of skeletal tissue.