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Wnt7b can replace Ihh to induce hypertrophic cartilage vascularization but not osteoblast differentiation during endochondral bone development.

Joeng KS, Long F - Bone Res (2014)

Bottom Line: Indian hedgehog (Ihh) is an essential signal that regulates endochondral bone development.Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh(-/-); Gli3(-/-) embryo.Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Washington University School of Medicine , St Louis, MO, USA ; Division of Biology and Biomedical Sciences, Washington University in St. Louis , St Louis, MO, USA.

ABSTRACT
Indian hedgehog (Ihh) is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh(-/-) mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh(-/-) mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh(-/-); Gli3(-/-) embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development.

No MeSH data available.


Related in: MedlinePlus

Wnt7b increases bone formation during endochondral bone development. (a, b) Whole-mount skeletal staining of E18.5 embryos from R26Wnt7b/+ (a) versus Col2-Cre3; R26Wnt7b/+ (b) embryos. Arrows point to tibia that show marked size difference. (c, d) H&E staining of longitudinal sections through the distal half of humerus. (c1, d1) Higher magnification of boxed regions shown in c and d. Green line in c1, d1 denotes cortical thickness.
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fig2: Wnt7b increases bone formation during endochondral bone development. (a, b) Whole-mount skeletal staining of E18.5 embryos from R26Wnt7b/+ (a) versus Col2-Cre3; R26Wnt7b/+ (b) embryos. Arrows point to tibia that show marked size difference. (c, d) H&E staining of longitudinal sections through the distal half of humerus. (c1, d1) Higher magnification of boxed regions shown in c and d. Green line in c1, d1 denotes cortical thickness.

Mentions: To study the role of Wnt7b on bone formation, we took advantage of the R26-Wnt7b mouse strain that can overexpress Wnt7b in a Cre-dependent manner.12 Specifically, we generated Col2-Cre3;R26Wnt7b/+ mice (termed C2Wnt7b mice) by using the Col2-Cre3 transgenic line that targets both osteoblasts and chondrocytes.3 Whole-mount skeletal staining at E18.5 indicated that the long bones in C2Wnt7b embryos were slightly shorter but noticeably thicker than those in the normal littermate with the genotype of R26Wnt7b/+ (Figure 2a and b). Histological analyses showed not only an increase in the thickness of the cortical bone, but also a presumptive marrow cavity filled with bone in the C2Wnt7b animal (Figure 2c, 2c1, 2d and 2d1). On the other hand, the growth plate cartilage appeared to be relatively normal. Consistent with histology showing extra bone mass within the presumptive marrow cavity of C2Wnt7b mice, in situ hybridization confirmed that the area contained an abnormally large number of osteoblasts expressing the well-known markers including Osterix (Osx), bone sialoprotein (Bsp), and osteocalcin (OC) (Figure 3). These results confirm that the R26–Wnt7b mouse strain is functional and that Wnt7b stimulates bone formation in the mouse embryo.


Wnt7b can replace Ihh to induce hypertrophic cartilage vascularization but not osteoblast differentiation during endochondral bone development.

Joeng KS, Long F - Bone Res (2014)

Wnt7b increases bone formation during endochondral bone development. (a, b) Whole-mount skeletal staining of E18.5 embryos from R26Wnt7b/+ (a) versus Col2-Cre3; R26Wnt7b/+ (b) embryos. Arrows point to tibia that show marked size difference. (c, d) H&E staining of longitudinal sections through the distal half of humerus. (c1, d1) Higher magnification of boxed regions shown in c and d. Green line in c1, d1 denotes cortical thickness.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472126&req=5

fig2: Wnt7b increases bone formation during endochondral bone development. (a, b) Whole-mount skeletal staining of E18.5 embryos from R26Wnt7b/+ (a) versus Col2-Cre3; R26Wnt7b/+ (b) embryos. Arrows point to tibia that show marked size difference. (c, d) H&E staining of longitudinal sections through the distal half of humerus. (c1, d1) Higher magnification of boxed regions shown in c and d. Green line in c1, d1 denotes cortical thickness.
Mentions: To study the role of Wnt7b on bone formation, we took advantage of the R26-Wnt7b mouse strain that can overexpress Wnt7b in a Cre-dependent manner.12 Specifically, we generated Col2-Cre3;R26Wnt7b/+ mice (termed C2Wnt7b mice) by using the Col2-Cre3 transgenic line that targets both osteoblasts and chondrocytes.3 Whole-mount skeletal staining at E18.5 indicated that the long bones in C2Wnt7b embryos were slightly shorter but noticeably thicker than those in the normal littermate with the genotype of R26Wnt7b/+ (Figure 2a and b). Histological analyses showed not only an increase in the thickness of the cortical bone, but also a presumptive marrow cavity filled with bone in the C2Wnt7b animal (Figure 2c, 2c1, 2d and 2d1). On the other hand, the growth plate cartilage appeared to be relatively normal. Consistent with histology showing extra bone mass within the presumptive marrow cavity of C2Wnt7b mice, in situ hybridization confirmed that the area contained an abnormally large number of osteoblasts expressing the well-known markers including Osterix (Osx), bone sialoprotein (Bsp), and osteocalcin (OC) (Figure 3). These results confirm that the R26–Wnt7b mouse strain is functional and that Wnt7b stimulates bone formation in the mouse embryo.

Bottom Line: Indian hedgehog (Ihh) is an essential signal that regulates endochondral bone development.Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh(-/-); Gli3(-/-) embryo.Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Washington University School of Medicine , St Louis, MO, USA ; Division of Biology and Biomedical Sciences, Washington University in St. Louis , St Louis, MO, USA.

ABSTRACT
Indian hedgehog (Ihh) is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh(-/-) mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh(-/-) mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh(-/-); Gli3(-/-) embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development.

No MeSH data available.


Related in: MedlinePlus