Dataset Information

BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint.

ABSTRACT:

Objective

Bone morphogenetic protein 2 (BMP2) plays important roles in cartilage growth and development. Paradoxically, elevated levels of BMP2 leads to hypertrophic differentiation and osteoarthritis of cartilage. We examined the in vivo loss of BMP2 in cells expressing aggrecan of the mandibular condyle and knee.

Design

Three-week-old BMP2 flox/flox-CreER-positive mice and their Cre-negative littermates were treated with tamoxifen and raised until 3 or 6 months. We also investigated the direct effects of BMP2 on chondrocytes in vitro. Cells from the mandibular condyle of mice were treated with recombinant human BMP2 (rhBMP2) or rhNoggin (inhibitor of BMP2 signaling).

Results

Conditional deletion of BMP2 caused breakage of the cartilage integrity in the mandibular condyle of mice from both age groups, accompanied by a decrease in cartilage thickness, matrix synthesis, mineralization, chondrocyte proliferation, and increased expression of degeneration markers, while the effects at articular cartilage were not significant. In vitro results revealed that rhBMP2 increased chondrocyte proliferation, mineralization, and differentiation, while noggin induced opposite effects.

Conclusions

In conclusion, BMP2 is essential for postnatal maintenance of the osteochondral tissues of the mandibular condyle.

SUBMITTER: O'Brien MH

PROVIDER: S-EPMC8804803 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint.

O'Brien Mara H MH Dutra Eliane H EH Mehta Shivam S Chen Po-Jung PJ Yadav Sumit S

Cartilage 20201214 2_suppl

<h4>Objective</h4>Bone morphogenetic protein 2 (BMP2) plays important roles in cartilage growth and development. Paradoxically, elevated levels of BMP2 leads to hypertrophic differentiation and osteoarthritis of cartilage. We examined the <i>in vivo</i> loss of BMP2 in cells expressing aggrecan of the mandibular condyle and knee.<h4>Design</h4>Three-week-old <i>BMP2 flox/flox</i>-<i>CreER</i>-positive mice and their Cre-negative littermates were treated with tamoxifen and raised until 3 or 6 mon ...[more]

PMID: 33307770

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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

BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint.

Objective

Design

Results

Conclusions

Publications

BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint.

Similar Datasets

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