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Updated: Jun 17, 2026
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in
Tripti Gaur1, Sadiq Hussain, Rajini Mudhasani
1Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Abstract:
MicroRNA attenuation of protein translation has emerged as an important regulator of mesenchymal cell differentiation into the osteoblast lineage. A compelling question is the extent to which miR biogenesis is obligatory for bone formation. Here we show conditional deletion of the Dicer enzyme in osteoprogenitors by Col1a1-Cre compromised fetal survival after E14.5. A mechanism was associated with the post-commitment stage of osteoblastogenesis, demonstrated by impaired ECM mineralization and reduced expression of mature osteoblast markers during differentiation of mesenchymal cells of ex vivo deleted Dicer(c/c). In contrast, in vivo excision of Dicer by Osteocalcin-Cre in mature osteoblasts generated a viable mouse with a perinatal phenotype of delayed bone mineralization which was resolved by 1 month. However, a second phenotype of significantly increased bone mass developed by 2 months, which continued up to 8 months in long bones and vertebrae, but not calvariae. Cortical bone width and trabecular thickness in Dicer(Deltaoc/Deltaoc) was twice that of Dicer(c/c) controls. Normal cell and tissue organization was observed. Expression of osteoblast and osteoclast markers demonstrated increased coupled activity of both cell types. We propose that Dicer generated miRs are essential for two periods of bone formation, to promote osteoblast differentiation before birth, and control bone accrual in the adult.
Insights
MicroRNA biogenesis, regulated by Dicer, is essential for bone formation. Deleting Dicer impairs fetal osteoblast differentiation and causes increased bone mass in adult mice, highlighting its dual role in bone development and maintenance.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- MicroRNAs (miRNAs) regulate protein translation and are crucial for mesenchymal cell differentiation into osteoblasts.
- The necessity of miRNA biogenesis for bone formation remains an open question in skeletal biology.
Purpose of the Study:
- To investigate the role of Dicer-dependent miRNA biogenesis in osteoblast differentiation and bone formation.
- To determine the impact of Dicer deletion at different stages of osteoblastogenesis on skeletal development and adult bone mass.
Main Methods:
- Conditional deletion of the Dicer enzyme in osteoprogenitors using Col1a1-Cre and in mature osteoblasts using Osteocalcin-Cre.
- Ex vivo differentiation of mesenchymal cells with deleted Dicer.
- In vivo analysis of fetal survival, perinatal bone mineralization, and adult bone mass in Dicer conditional knockout mice.
- Histological analysis of bone structure and assessment of osteoblast and osteoclast marker expression.
Main Results:
- Conditional deletion of Dicer in osteoprogenitors (Col1a1-Cre) led to compromised fetal survival and impaired osteoblast differentiation with reduced ECM mineralization.
- In vivo deletion of Dicer in mature osteoblasts (Osteocalcin-Cre) resulted in transient perinatal bone mineralization delay, followed by a significant increase in bone mass in adults.
- Adult mice with Dicer deleted in mature osteoblasts exhibited doubled cortical bone width and trabecular thickness, with increased coupled osteoblast and osteoclast activity.
Conclusions:
- Dicer-generated miRNAs are essential for promoting osteoblast differentiation during fetal development.
- Dicer-dependent miRNAs play a critical role in regulating bone accrual and maintaining bone mass in adult organisms.
- These findings underscore the dual importance of miRNA biogenesis in both embryonic skeletal formation and adult bone homeostasis.
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