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Updated: May 11, 2026
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Pin1 null mice exhibit low bone mass and attenuation of BMP signaling
Zhong-Jian Shen1, Jie Hu, Aktar Ali
1Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America. zhong.shen@UTSouthwestern.edu
Abstract:
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.
Insights
The peptidyl-prolyl isomerase PIN1 regulates osteoblast activity. Pin1 deficiency impairs bone formation by affecting BMP signaling and key gene expression, revealing PIN1 as a therapeutic target for bone diseases.
Area of Science:
- Molecular biology
- Bone biology
- Biochemistry
Background:
- Bone remodeling involves osteoblasts and osteoclasts.
- Molecular mechanisms of osteoblast function are not fully understood.
Purpose of the Study:
- To investigate the role of peptidyl-prolyl isomerase PIN1 in osteoblast function.
- To identify PIN1 as a potential therapeutic target for bone diseases.
Main Methods:
- Analysis of Pin1 null mice.
- Assessment of bone mineral density and bone formation.
- Investigation of BMP signaling pathways.
- Examination of osteoblast-specific gene expression and extracellular matrix production.
Main Results:
- Pin1 null mice showed decreased bone mineral density and trabecular bone formation.
- Osteoblasts from Pin1 null mice had impaired BMP signaling.
- PIN1 interacted with SMAD5 and was essential for osteoblast-specific gene expression (CBFA1, OSX), ECM production (collagen I, OCN), and bone nodule formation.
Conclusions:
- PIN1 is a critical regulator of osteoblast osteogenic activity.
- PIN1 controls bone formation through BMP signaling and transcription factor expression.
- Targeting PIN1 may offer a novel therapeutic strategy for bone diseases.
