Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: KEGG:D03301 (
PDL
)
658
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pyrophosphate (PP
i
) serves as a potent and physiologically important regulator of mineralization, with systemic and local concentrations determined by several key regulators, including: tissue-nonspecific alkaline phosphatase (ALPL gene;
TNAP
protein), the progressive ankylosis protein (ANKH; ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; ENPP1). Results to date have indicated important roles for PP
i
in cementum formation, and we addressed several gaps in knowledge by employing genetically edited mouse models where PP
i
metabolism was disrupted and pharmacologically modulating PP
i
in a PP
i
-deficient mouse model. We demonstrate that acellular cementum growth is inversely proportional to PP
i
levels, with reduced cementum in Alpl KO (increased PP
i
levels) mice and excess cementum in Ank KO mice (decreased PP
i
levels). Moreover, simultaneous ablation of Alpl and Ank results in reestablishment of functional cementum in dKO mice. Additional reduction of PP
i
by dual deletion of Ank and Enpp1 does not further increase cementogenesis, and
PDL
space is maintained in part through bone modeling/remodeling by osteoclasts. Our results provide insights into cementum formation and expand our knowledge of how PP
i
regulates cementum. We also demonstrate for the first time that pharmacologic manipulation of PP
i
through an ENPP1-Fc fusion protein can regulate cementum growth, supporting therapeutic interventions targeting PP
i
metabolism.
...
PMID:Genetic and pharmacologic modulation of cementogenesis via pyrophosphate regulators. 3222 62
