TGF beta receptor II interacting protein-1, an intracellular protein has an extracellular role as a modulator of matrix mineralization
| Autor: | Sriram Ravindran, Amsaveni Ramachandran, Chun-Chieh Huang, Anne George |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Calcium Phosphates Male Eukaryotic Initiation Factor-3 chemistry.chemical_element Mice Nude Calcium Exosomes Collagen Type I Article Cell Line Extracellular matrix 03 medical and health sciences Calcification Physiologic Osteogenesis Extracellular Animals Humans Eukaryotic Initiation Factors R-SMAD Multidisciplinary Osteoblasts 030102 biochemistry & molecular biology Chemistry Skull Intracellular Signaling Peptides and Proteins Cell Differentiation Endoglin TGF beta receptor 2 Cell biology Extracellular Matrix Rats 030104 developmental biology Alkaline phosphatase human activities Intracellular |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Transforming growth factor beta receptor II interacting protein 1 (TRIP-1), a predominantly intracellular protein is localized in the ECM of bone. TRIP-1 lacks a signal peptide, therefore, in this study, we provide evidence that intracellular TRIP-1 can be packaged and exported to the ECM via exosomes. Overexpression of TRIP-1 in MC3T3-E1 cells resulted in increased matrix mineralization during differentiation and knockdown resulted in reduced effects. In vivo function of TRIP-1 was studied by an implantation assay performed using TRIP-1 overexpressing and knockdown cells cultured in a 3-dimmensional scaffold. After 4 weeks, the subcutaneous tissues from TRIP-1 overexpressing cells showed higher calcium and phosphate deposits, arranged collagen fibrils and increased expression of Runx2 and alkaline phosphatase. Nucleation studies on demineralized and deproteinized dentin wafer is a powerful tool to determine the functional role of noncollagenous proteins in matrix mineralization. Using this system, we provide evidence that TRIP-1 binds to Type-I collagen and can promote mineralization. Surface plasmon resonance analysis demonstrated that TRIP-1 binds to collagen with KD = 48 μM. SEM and TEM analysis showed that TRIP-1 promoted the nucleation and growth of calcium phosphate mineral aggregates. Taken together, we provide mechanistic insights of this intracellular protein in matrix mineralization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|