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Disruption of Scube2 Impairs Indian Hedgehog‐mediated Osteoblast Differentiation
Author(s) -
Lin YuhCharn,
Yan YuTing,
Yang RueyBing
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.726.5
Subject(s) - osteoblast , microbiology and biotechnology , endochondral ossification , progenitor cell , mesenchymal stem cell , zebrafish , hedgehog , hedgehog signaling pathway , indian hedgehog , signal transduction , chondrocyte , cellular differentiation , biology , endocrinology , sonic hedgehog , smoothened , medicine , chemistry , cartilage , stem cell , in vitro , anatomy , genetics , gene
SCUBE2 (signal peptide‐CUB‐EGF domain‐containing protein 2) belongs to a secreted and membrane‐tethered multi‐domain SCUBE protein family composed of 3 members found in vertebrates and mammals. Recent reports suggested that zebrafish scube2 could facilitate sonic hedgehog (SHH) signaling for proper development of slow muscle. However, whether SCUBE2 can regulate the signaling activity of two other HH ligands (IHH and DHH), and the developmental relevance of the SCUBE2‐induced HH signaling in mammals remain poorly understood. In this study, we first showed that as compared with SCUBE1 or 3, SCUBE2 is the most potent modulator of IHH signaling in vitro . In addition, gain and loss‐of‐function studies demonstrated that SCUBE2 exerted an osteogenic function by enhancing IHH‐stimulated osteoblast differentiation in the mouse mesenchymal progenitor cells. Consistent with these in vitro studies and the prominent roles of Ihh in coordinating skeletogenesis, genetic ablation of Scube2 (‐/‐) caused defective endochondral bone formation and impaired IHH‐mediated osteoblast differentiation of ‐/‐ bone‐marrow mesenchymal stromal‐cell cultures. Our data demonstrate that Scube2 plays a key regulatory role in IHH‐stimulated osteoblast differentiation during endochondral bone formation.