Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 50, Pages 18023-18027Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503617102
Keywords
bone morphogenetic protein receptor 1A; bone morphogenetic protein receptor 1B; bone morphogenetic protein; chondrocyte differentiation; transgenic
Categories
Funding
- NIAMS NIH HHS [AR44528, R01 AR044528] Funding Source: Medline
- NIDDK NIH HHS [P01 DK56246, P01 DK056246] Funding Source: Medline
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Bone morphogenetic proteins (BMPs) play important roles at multiple stages of endochondral bone formation. However, the roles of BMP signaling in chondrocytes in vivo are still contentious. In the present study, we overexpressed a constitutively active BMP receptor 1A (caBmpr1a) in chondrocytes by using two systems: caBmpr1a was directly driven by a rat type II collagen promoter in a conventional transgenic system and indirectly driven in a UAS-Gal4 binary system. CaBmpr1a expression caused shortening of the columnar layer of proliferating chondrocytes and up-regulation of maturation markers, suggesting acceleration of differentiation of proliferating chondrocytes toward hypertrophic chondrocytes. In addition to the acceleration of chondrocyte differentiation, conventional transgenic mice showed widening of cartilage elements and morphological alteration of perichondrial cells, possibly due to stimulation of differentiation of prechondrogenic cells. Moreover, bigenic expression of caBmpr1a rescued the differentiation defect of prechondrogenic cells in Bmpr1b-null phalanges. This finding indicates that BMP signaling is necessary for phalangeal prechondrogenic cells to differentiate into chondrocytes and that signaling of BMP receptor 1B in this context is replaceable by that of a constitutively active BMP receptor 1A. These results suggest that BMP signaling in prechondrogenic cells and in growth plate chondrocytes stimulates their chondrocytic differentiation and maturation toward hypertrophy, respectively.
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