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Mice that lack sclerostin also lack B cells


Sost knockout mice (Sost−/− mice) cannot produce sclerostin and therefore provide a good model of sclerosteosis with which to investigate the impact of the disease on bone marrow. Cain et al. analyzed the bone microenvironment of Sost−/− mice, showing that the bone marrow contained very few B cells due to elevated apoptosis of all B cell progenitors. Sost expression in wild type animals is high in osteocytes but the gene is quiet in hematopoietic stem cells, so it was no surprise that normal B cell function was observed in the spleens of Sost−/− mice.

CXCL12 (also called SDF-1), a growth stimulating factor that acts on B cell progenitors, was found at significantly lower levels in bone marrow stromal cells from Sost−/− mice compared to wild type mice. This suggested that the lower number of B cells in the mouse model was due to a non-cell autonomous effect, and this was confirmed by reciprocal bone marrow transplants. The increased CXCL12 was found to promote B cell differentiation and survival via binding to the receptor CXCR4.

Editor's comment: According to this study, osteocyte-secreted sclerostin enhances CXCL12 (SDF-1) production via inhibition of Wnt signaling in bone marrow stromal cells. This study raises the possibility that enhancing Wnt signaling in osteoblasts through inhibition of sclerostin action may suppress B cell development.

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