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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

Expression of Wnt7b in developing long bones of mouse embryos. (a1, a2, b1, b2) H&E staining (a1, b1) and Wnt7b in situ hybridization (a2, b2) on longitudinal sections of the humerus in WT embryos at E15.5 (a1, a2) and E18.5 (b1, b2). (c1, c2, d1, d2) H&E staining (c1, d1) and Wnt7b in situ hybridization (c2, d2) on longitudinal sections of the humerus in Ihh−/− embryos at E15.5 (c1, c2) and E18.5 (d1, d2). In situ hybridization signal in red. Arrows denote expression in perichondrium flanking prehypertrophic and early hypertrophic cartilage. WT, wild-type.
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fig1: Expression of Wnt7b in developing long bones of mouse embryos. (a1, a2, b1, b2) H&E staining (a1, b1) and Wnt7b in situ hybridization (a2, b2) on longitudinal sections of the humerus in WT embryos at E15.5 (a1, a2) and E18.5 (b1, b2). (c1, c2, d1, d2) H&E staining (c1, d1) and Wnt7b in situ hybridization (c2, d2) on longitudinal sections of the humerus in Ihh−/− embryos at E15.5 (c1, c2) and E18.5 (d1, d2). In situ hybridization signal in red. Arrows denote expression in perichondrium flanking prehypertrophic and early hypertrophic cartilage. WT, wild-type.

Mentions: Previously, in E14.5 mouse embryos, we have shown that Wnt7b is expressed by perichondral cells flanking the prehypertrophic and early hypertrophic cartilage, and that the expression is critically dependent on Ihh signaling. To corroborate this finding, we performed in situ hybridization on long bone sections from mouse embryos of later stages. At E15.5, Wnt7b was normally expressed most robustly in the perichondrium flanking the prehypertrophic and early hypertrophic chondrocytes, but also at a lower level in the perichondrium/periosteum flanking the emerging marrow cavity (Figure 1a1 and 1a2). Interestingly, at E18.5, Wnt7b expression was more restricted to the perichondrium surrounding the prehypertrophic and early hypertrophic chondrocytes, with no obvious expression in the diaphyseal periosteum (Figure 1b1 and 1b2). In contrast, Wnt7b was not detected in Ihh−/− embryos at either stage (Figure 1c1, 1c2, 1d1 and 1d2). Thus, Wnt7b is expressed in the osteogenic perichondrium in an Ihh-dependent manner.


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

Joeng KS, Long F - Bone Res (2014)

Expression of Wnt7b in developing long bones of mouse embryos. (a1, a2, b1, b2) H&E staining (a1, b1) and Wnt7b in situ hybridization (a2, b2) on longitudinal sections of the humerus in WT embryos at E15.5 (a1, a2) and E18.5 (b1, b2). (c1, c2, d1, d2) H&E staining (c1, d1) and Wnt7b in situ hybridization (c2, d2) on longitudinal sections of the humerus in Ihh−/− embryos at E15.5 (c1, c2) and E18.5 (d1, d2). In situ hybridization signal in red. Arrows denote expression in perichondrium flanking prehypertrophic and early hypertrophic cartilage. WT, wild-type.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Expression of Wnt7b in developing long bones of mouse embryos. (a1, a2, b1, b2) H&E staining (a1, b1) and Wnt7b in situ hybridization (a2, b2) on longitudinal sections of the humerus in WT embryos at E15.5 (a1, a2) and E18.5 (b1, b2). (c1, c2, d1, d2) H&E staining (c1, d1) and Wnt7b in situ hybridization (c2, d2) on longitudinal sections of the humerus in Ihh−/− embryos at E15.5 (c1, c2) and E18.5 (d1, d2). In situ hybridization signal in red. Arrows denote expression in perichondrium flanking prehypertrophic and early hypertrophic cartilage. WT, wild-type.
Mentions: Previously, in E14.5 mouse embryos, we have shown that Wnt7b is expressed by perichondral cells flanking the prehypertrophic and early hypertrophic cartilage, and that the expression is critically dependent on Ihh signaling. To corroborate this finding, we performed in situ hybridization on long bone sections from mouse embryos of later stages. At E15.5, Wnt7b was normally expressed most robustly in the perichondrium flanking the prehypertrophic and early hypertrophic chondrocytes, but also at a lower level in the perichondrium/periosteum flanking the emerging marrow cavity (Figure 1a1 and 1a2). Interestingly, at E18.5, Wnt7b expression was more restricted to the perichondrium surrounding the prehypertrophic and early hypertrophic chondrocytes, with no obvious expression in the diaphyseal periosteum (Figure 1b1 and 1b2). In contrast, Wnt7b was not detected in Ihh−/− embryos at either stage (Figure 1c1, 1c2, 1d1 and 1d2). Thus, Wnt7b is expressed in the osteogenic perichondrium in an Ihh-dependent manner.

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