Pin1 null mice exhibit low bone mass and attenuation of BMP signaling. PLoS One 2013;8(5):e63565
Date
05/16/2013Pubmed ID
23675491Pubmed Central ID
PMC3651169DOI
10.1371/journal.pone.0063565Scopus ID
2-s2.0-84877601696 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Bone is constantly formed and resorbed throughout life by coordinated actions of osteoblasts and osteoclasts. However, the molecular mechanisms involved in osteoblast function remain incompletely understood. Here we show, for the first time, that the peptidyl-prolyl isomerase PIN1 controls the osteogenic activity of osteoblasts. Pin1 null mice exhibited an age-dependent decrease in bone mineral density and trabecular bone formation without alteration in cortical bone. Further analysis identified a defect in BMP signaling in Pin1 null osteoblasts but normal osteoclast function. PIN1 interacted with SMAD5 and was required for the expression by primary osteoblasts of osteoblast specific transcription factors (CBFA1 and OSX), ECM (collagen I and OCN) and the formation of bone nodules. Our results thus uncover a novel aspect of the molecular underpinning of osteoblast function and identify a new therapeutic target for bone diseases.
Author List
Shen ZJ, Hu J, Ali A, Pastor J, Shiizaki K, Blank RD, Kuro-o M, Malter JSMESH terms used to index this publication - Major topics in bold
AnimalsBone Density
Bone Development
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Bone and Bones
Calcium
Cell Differentiation
Cholecalciferol
Gene Expression
Mice
Mice, Knockout
NIMA-Interacting Peptidylprolyl Isomerase
Osteoclasts
Peptidylprolyl Isomerase
Protein Binding
Radiography
Signal Transduction
Smad5 Protein
