Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse

被引：128

作者：

Gaur, Tripti ^{[1
,2
]}

Hussain, Sadiq ^{[1
,2
]}

Mudhasani, Rajini ^{[1
,2
]}

Parulkar, Isha ^{[1
,2
]}

Colby, Jennifer L. ^{[1
,2
]}

Frederick, Dana ^{[1
,2
]}

Kream, Barbara E. ^{[3
]}

van Wijnen, Andre J. ^{[1
,2
]}

Stein, Janet L. ^{[1
,2
]}

Stein, Gary S. ^{[1
,2
]}

Jones, Stephen N. ^{[1
,2
]}

Lian, Jane B. ^{[1
,2
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA

[2] Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01655 USA

[3] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA

来源：

DEVELOPMENTAL BIOLOGY | 2010年 / 340卷 / 01期

关键词：

Dicer ablation; MicroRNAs; Bone formation; Col1a-Cre; Osteocalcin-Cre; High bone mass; Osteoblast differentiation; Bone development; ENZYME DICER; STEM-CELLS; LINEAGE COMMITMENT; TARGETED DELETION; TRABECULAR BONE; MORPHOGENESIS; EXPRESSION; MICE; OSTEOCYTES; MICRORNAS;

D O I：

10.1016/j.ydbio.2010.01.008

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(Delta oc/Delta oc) 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. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：10 / 21

页数：12