Dataset Information

BMP signaling stimulates cellular differentiation at multiple steps during cartilage development.

ABSTRACT: 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.

SUBMITTER: Kobayashi T

PROVIDER: S-EPMC1312369 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature

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BMP signaling stimulates cellular differentiation at multiple steps during cartilage development.

Kobayashi Tatsuya T Lyons Karen M KM McMahon Andrew P AP Kronenberg Henry M HM

Proceedings of the National Academy of Sciences of the United States of America 20051201 50

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 shor ...[more]

PMID: 16322106

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Project description:Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member) to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be investigated as a possible therapeutic strategy for maintaining the health of joint linings.

Dataset Information

BMP signaling stimulates cellular differentiation at multiple steps during cartilage development.

Publications

BMP signaling stimulates cellular differentiation at multiple steps during cartilage development.

Similar Datasets

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