Limits...
Chondrocyte-specific inhibition of β-catenin signaling leads to dysplasia of the caudal vertebrae in mice.

Shu B, Li TF, Li XF, Tang DZ, Zhang Y, Shi Q, Wang YJ, Chen D - Spine (2013)

Bottom Line: Inhibition of β-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process.Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae.Wnt/β-catenin signaling plays an important role in vertebral development.

View Article: PubMed Central - PubMed

Affiliation: *Spine Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China †Department of Biochemistry, Rush University Medical Center, Chicago, IL; and ‡Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

ABSTRACT

Study design: To inhibit β-catenin specifically signaling in chondrocytes Col2-ICAT transgenic mice were generated. Anomalies in caudal vertebrae were detected during embryonic and postnatal stages of Col2-ICAT transgenic mice.

Objective: To determine the role of canonical β-catenin signaling in caudal vertebral development.

Summary of background data: β-catenin signaling plays a critical role in skeletal development. Col2-ICAT transgenic mice were generated to selectively block β-catenin signaling by overexpression of the ICAT gene in chondrocytes.

Methods: Tails of E16.5 transgenic embryos and adult Col2-ICAT transgenic mice and their wild-type littermates were collected and analyzed. Skeletal preparation, 3-dimensional micro-computed tomographic and histological analyses were performed to evaluate changes in the structure of caudal vertebrae. Bromodeoxyuridine labeling was performed to evaluate changes in chondrocyte proliferation in caudal vertebrae.

Results: Skeletal preparation and 3-dimensional micro-computed tomographic analyses revealed bone deformation and angulated deformities in tail tissue in Col2-ICAT transgenic mice. Histological studies revealed abnormal bone development and dysplastic caudal vertebrae in Col2-ICAT transgenic mice. Inhibition of β-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process. Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae. BrdU labeling revealed a decreased chondrocyte proliferation in both cartilageous templates of transgenic embryos and the growth plate of adult Col2-ICAT transgenic mice.

Conclusion: Wnt/β-catenin signaling plays an important role in vertebral development. Inhibition of β-catenin signaling in chondrocytes results in caudal vertebra deformity in mice, which may occur as early as in the stage of sclerotome formation.

Level of evidence: N/A.

Show MeSH

Related in: MedlinePlus

Col2-ICAT transgenic mice display an aberrant vertebral development resulting in angulated deformity in tails as evidenced by macroscopic observation (A) and radiographic analysis (B). The results of whole-mount Alizarin red/Alcian blue staining showed abnormal bone formation in the tails of the Col2-ICAT transgenic mice (C). The results were further confirmed by micro-CT analysis (D). The quantitative data showed that numbers of caudal vertebrae of the Col2-ICAT transgenic mice were significantly reduced compared with the WT littermates (E). P < 0.05, unpaired Student t test (n = 6). WT indicates wild-type; CT, computed tomographic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928445&req=5

Figure 1: Col2-ICAT transgenic mice display an aberrant vertebral development resulting in angulated deformity in tails as evidenced by macroscopic observation (A) and radiographic analysis (B). The results of whole-mount Alizarin red/Alcian blue staining showed abnormal bone formation in the tails of the Col2-ICAT transgenic mice (C). The results were further confirmed by micro-CT analysis (D). The quantitative data showed that numbers of caudal vertebrae of the Col2-ICAT transgenic mice were significantly reduced compared with the WT littermates (E). P < 0.05, unpaired Student t test (n = 6). WT indicates wild-type; CT, computed tomographic.

Mentions: The mice were able to ambulate and move their tails, suggesting that the neural tube development had not been affected. We observed that all Col2-ICAT transgenic mice developed at least one angulated deformity in their distal tails (Figure 1A). Radiographical images showed an aberrant vertebral development, leading to reduced lengths of the caudal vertebrae (Figure 1B). Skeletal preparation and 3-dimensional (3D) reconstruction analyses showed the paraxial locations of the sesamoid-like bones in most transgenic mice. The deformed bones were either solitary or attached to neighboring vertebra, and in some cases, single or multiple bones with different sizes were dislocated on the opposite side (Figure 1C, D). All Col2-ICAT transgenic mice showed decreased numbers of the caudal vertebrae compared with their WT littermates (Figure 1E, unpaired Student t test, * P < 0.05, n = 6).


Chondrocyte-specific inhibition of β-catenin signaling leads to dysplasia of the caudal vertebrae in mice.

Shu B, Li TF, Li XF, Tang DZ, Zhang Y, Shi Q, Wang YJ, Chen D - Spine (2013)

Col2-ICAT transgenic mice display an aberrant vertebral development resulting in angulated deformity in tails as evidenced by macroscopic observation (A) and radiographic analysis (B). The results of whole-mount Alizarin red/Alcian blue staining showed abnormal bone formation in the tails of the Col2-ICAT transgenic mice (C). The results were further confirmed by micro-CT analysis (D). The quantitative data showed that numbers of caudal vertebrae of the Col2-ICAT transgenic mice were significantly reduced compared with the WT littermates (E). P < 0.05, unpaired Student t test (n = 6). WT indicates wild-type; CT, computed tomographic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928445&req=5

Figure 1: Col2-ICAT transgenic mice display an aberrant vertebral development resulting in angulated deformity in tails as evidenced by macroscopic observation (A) and radiographic analysis (B). The results of whole-mount Alizarin red/Alcian blue staining showed abnormal bone formation in the tails of the Col2-ICAT transgenic mice (C). The results were further confirmed by micro-CT analysis (D). The quantitative data showed that numbers of caudal vertebrae of the Col2-ICAT transgenic mice were significantly reduced compared with the WT littermates (E). P < 0.05, unpaired Student t test (n = 6). WT indicates wild-type; CT, computed tomographic.
Mentions: The mice were able to ambulate and move their tails, suggesting that the neural tube development had not been affected. We observed that all Col2-ICAT transgenic mice developed at least one angulated deformity in their distal tails (Figure 1A). Radiographical images showed an aberrant vertebral development, leading to reduced lengths of the caudal vertebrae (Figure 1B). Skeletal preparation and 3-dimensional (3D) reconstruction analyses showed the paraxial locations of the sesamoid-like bones in most transgenic mice. The deformed bones were either solitary or attached to neighboring vertebra, and in some cases, single or multiple bones with different sizes were dislocated on the opposite side (Figure 1C, D). All Col2-ICAT transgenic mice showed decreased numbers of the caudal vertebrae compared with their WT littermates (Figure 1E, unpaired Student t test, * P < 0.05, n = 6).

Bottom Line: Inhibition of β-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process.Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae.Wnt/β-catenin signaling plays an important role in vertebral development.

View Article: PubMed Central - PubMed

Affiliation: *Spine Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China †Department of Biochemistry, Rush University Medical Center, Chicago, IL; and ‡Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

ABSTRACT

Study design: To inhibit β-catenin specifically signaling in chondrocytes Col2-ICAT transgenic mice were generated. Anomalies in caudal vertebrae were detected during embryonic and postnatal stages of Col2-ICAT transgenic mice.

Objective: To determine the role of canonical β-catenin signaling in caudal vertebral development.

Summary of background data: β-catenin signaling plays a critical role in skeletal development. Col2-ICAT transgenic mice were generated to selectively block β-catenin signaling by overexpression of the ICAT gene in chondrocytes.

Methods: Tails of E16.5 transgenic embryos and adult Col2-ICAT transgenic mice and their wild-type littermates were collected and analyzed. Skeletal preparation, 3-dimensional micro-computed tomographic and histological analyses were performed to evaluate changes in the structure of caudal vertebrae. Bromodeoxyuridine labeling was performed to evaluate changes in chondrocyte proliferation in caudal vertebrae.

Results: Skeletal preparation and 3-dimensional micro-computed tomographic analyses revealed bone deformation and angulated deformities in tail tissue in Col2-ICAT transgenic mice. Histological studies revealed abnormal bone development and dysplastic caudal vertebrae in Col2-ICAT transgenic mice. Inhibition of β-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process. Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae. BrdU labeling revealed a decreased chondrocyte proliferation in both cartilageous templates of transgenic embryos and the growth plate of adult Col2-ICAT transgenic mice.

Conclusion: Wnt/β-catenin signaling plays an important role in vertebral development. Inhibition of β-catenin signaling in chondrocytes results in caudal vertebra deformity in mice, which may occur as early as in the stage of sclerotome formation.

Level of evidence: N/A.

Show MeSH
Related in: MedlinePlus