The role and potential mechanism of p75NTR in mineralization via in vivo p75NTR knockout mice and in vitro ectomesenchymal stem cells

OBJECTIVE: The aim of this study is to investigate the role and potential mechanism of p75NTR in mineralization in vivo using p75NTR-knockout mice and in vitro using ectomesenchymal stem cells (EMSCs). MATERIALS AND METHODS: Femur bone mass and daily incisor mineralization speed were assessed in an in vivo p75NTR-knockout mouse model. The molecular signatures alkaline phosphatase (ALP), collagen type 1 (Col1), melanoma-associated antigen (Mage)-D1, bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), distal-less homeobox 1 (Dlx1) and Msh homeobox 1 (Msx1) were examined in vitro in EMSCs isolated from p75NTR(+/+) and p75NTR(ExIII-/-) mice. RESULTS: p75NTR-knockout mice were smaller in body size than heterozygous and wild-type mice. Micro-computed tomography and structural quantification showed that the osteogenic ability of p75NTR(ExIII) -knockout mice was significantly decreased compared with that of wild-type mice (P < .05). Weaker ALP and alizarin red staining and reduced expression of ALP, Col1, Runx2, BSP, OCN and OPN were also observed in p75NTR(ExIII-/-) EMSCs. Moreover, the distance between calcein fluorescence bands in p75NTR(ExIII) -knockout mice was significantly smaller than that in wild type and heterozygous mice (P < .05), indicating the lower daily mineralization speed of incisors in p75NTR(ExIII) -knockout mice. Further investigation revealed a positive correlation between p75NTR and Mage-D1, Dlx1, and Msx1. CONCLUSION: p75NTR not only promotes osteogenic differentiation and tissue mineralization, but also shows a possible relationship with the circadian rhythm of dental hard tissue formation.