Fig. 7

TGF-β1 as a key regulator of odontoblast differentiation and tooth root formation. Schematic diagram of the working hypothesis: TGF-β1 is released from bone matrix in response to osteoclastic bone resorption, and acts as a coupling growth factor in inducing radicular odontoblast differentiation and tooth root formation. TGF-β signaling plays an important role in regulating radicular odontoblast differentiation through affecting the expression of downstream targets (Nfic, Osx, Dspp and Nestin) in the process of root development. Particularly, TGF-β1 not only mediates OC-osteoblast communication and promotes bone formation, but also functions as an OC-odontoblast coupling factor which plays direct regulatory roles on odontoblasts, HERS, and may also on dental MSCs and eventually induces odontoblast differentiation and root formation. On the other hand, osteoclast loss/dysfunction often leads to osteopetrosis-associated root dysplasia resulted from impaired TGF-β1-mediated OC-odontoblast coupling in tooth root development. HERS, Hertwig’s epithelial root sheath