Abstract
We previously identified the novel gene, periodontal ligament-associated protein-1 (PLAP-1)/asporin and reported that PLAP-1/asporin inhibited bone morphogenetic protein-2 (BMP-2)-induced cytodifferentiation of periodontal ligament (PDL) cells probably by direct interaction with BMP-2. Here, we elucidated the detailed regulatory mechanism of this protein on BMP-2-induced cytodifferentiation of PDL cells. Recombinant PLAP-1/asporin inhibited BMP-2-induced cytodifferentiation of PDL cells and competitively prevented BMP-2 from binding to the BMP receptor-IB (BMPR-IB), resulting in inhibition of BMP-dependent activation of Smad proteins. The induction of mutation to the leucine-rich repeat (LRR) motif, especially LRR5, within PLAP-1/asporin rescued the inhibitory effect of PLAP-1/asporin on BMP-2. By contrast, a 26-amino acid peptide in the PLAP-1/asporin LRR5 sequence inhibited BMP-2 activity. Our findings indicate that PLAP-1/asporin inhibits BMP-2-induced differentiation of PDL cells resulting from inactivation of the BMP-2 signaling pathway and that LRR, especially LRR5 of PLAP-1/asporin, plays an important role in the PLAP-1/asporin-BMP-2 interaction.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Motifs / genetics
-
Animals
-
Bone Morphogenetic Protein 2
-
Bone Morphogenetic Protein Receptors, Type I / antagonists & inhibitors*
-
Bone Morphogenetic Protein Receptors, Type I / metabolism
-
Bone Morphogenetic Proteins / antagonists & inhibitors
-
Bone Morphogenetic Proteins / metabolism*
-
Bone Morphogenetic Proteins / pharmacology
-
Cell Differentiation / drug effects
-
Cell Differentiation / genetics
-
Cell Line
-
Extracellular Matrix Proteins / genetics
-
Extracellular Matrix Proteins / metabolism*
-
Extracellular Matrix Proteins / pharmacology
-
Leucine / chemistry
-
Mice
-
Mutation
-
Phosphorylation
-
Protein Conformation
-
Protein Interaction Domains and Motifs* / genetics
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Recombinant Proteins / pharmacology
-
Repetitive Sequences, Amino Acid / genetics
-
Smad Proteins / metabolism
-
Structure-Activity Relationship
-
Transforming Growth Factor beta / antagonists & inhibitors
-
Transforming Growth Factor beta / metabolism*
-
Transforming Growth Factor beta / pharmacology
Substances
-
Aspn protein, mouse
-
Bmp2 protein, mouse
-
Bone Morphogenetic Protein 2
-
Bone Morphogenetic Proteins
-
Extracellular Matrix Proteins
-
Recombinant Proteins
-
Smad Proteins
-
Transforming Growth Factor beta
-
Bone Morphogenetic Protein Receptors, Type I
-
Leucine