Abstract
ABSTRACTDentinogenesis, a formation of dentin by odontoblasts, is an essential process during tooth development. Bone morphogenetic proteins (BMPs) are one of the most crucial growth factors that contribute to dentin formation. However, it is still unclear how BMP signaling pathways regulate postnatal crown and root dentinogenesis. BMPs transduce signals through canonical Smad and non‐Smad signaling pathways including p38 and ERK signaling pathways. To investigate the roles of Smad and non‐Smad signaling pathways in dentinogenesis, we conditionally deleted Bmpr1a, which encodes the type 1A receptor for BMPs, to remove both Smad and non‐Smad pathways in Osterix‐expressing cells. We also expressed a constitutively activated form of Bmpr1a (caBmpr1a) to increase Smad1/5/9 signaling activity without altered non‐Smad activity in odontoblasts. To understand the function of BMP signaling during postnatal dentin formation, Cre activity was induced at the day of birth. Our results showed that loss of BmpR1A in odontoblasts resulted in impaired dentin formation and short molar roots at postnatal day 21. Bmpr1a cKO mice displayed a reduction of dentin matrix production compared to controls associated with increased cell proliferation and reduced Osx and Dspp expression. In contrast, caBmpr1a mutant mice that show increased Smad1/5/9 signaling activity resulted in no overt tooth phenotype. To further dissect the functions of each signaling activity, we generated Bmpr1a cKO mice also expressing caBmpr1a to restore only Smad1/5/9 signaling activity. Restoring Smad activity in the compound mutant mice rescued impaired crown dentin formation in the Bmpr1a cKO mice; however, impaired root dentin formation and short roots were not changed. These results suggest that BMP‐Smad signaling in odontoblasts is responsible for crown dentin formation, while non‐Smad signaling may play a major role in root dentin formation and elongation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Highlights
Dentinogenesis begins at the late bell stage of tooth development
Osx potentially marks dental mesenchymal progenitors that differentiate into odontoblasts and produce mineralized dentin matrix.[6,18] We noticed that conditional disruption of Bmpr1a using a constitutively active Osx-Cre results in embryonic lethality and we decided to use an inducible (Tet-off) system to activate Cre activity during postnatal development
Our findings demonstrate that loss of Bone morphogenetic proteins (BMPs) signaling in odontoblasts results in impaired crown and root dentin formation, and short roots associated with reduced Osx and Dspp expression
Summary
Odontoblasts, the cells of mesenchymal origin, located underneath the enamel, play an essential role in dentin formation. Dentin is classified as primary, secondary, and tertiary dentin by their location, timing of development, and histological characteristics.[1] Primary dentin is formed during early tooth development, whereas secondary dentin is produced after the tooth becomes functional. Tertiary dentin is secreted in response to external stimulation such as cavities and wear. The tertiary dentin produced by pre-existing or newly differentiated odontoblasts is deposited rapidly with irregular tubular patterns and some cellular inclusions called osteodentin. Recent studies provide evidence that formation of crown and root undergoes distinct cellular and molecular regulatory mechanisms.[2,3] it is not well understood whether odontoblasts residing in either crown or root have unique site-specific functions in dentinogenesis
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