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

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.

Bone development: Bringing in the blood vessels

Recent work has clarified the roles of two regulatory proteins in the multi-step process of fetal bone development. Bones are generated through the gradual transformation of cartilage into bone, and the development of blood vessels within the cartilage is a key step in this process. The signaling protein Ihh induces multiple steps in bone development, such as bone cell maturation and blood vessel formation, but how its many effects are mediated has not been clear. A group led by Fanxin Long at Washington University School of Medicine, USA, showed that the regulatory protein Wnt7b could induce blood vessel formation in the cartilage of animals lacking Ihh. However, it could not carry out all the other functions of Ihh. The findings show how regulatory proteins work together to induce specific aspects of bone development.

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