PUBLICATION
Disruption of Scube2 impairs endochondral bone formation
- Authors
- Lin, Y.C., Roffler, S.R., Yan, Y.T., Yang, R.B.
- ID
- ZDB-PUB-150203-7
- Date
- 2015
- Source
- Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 30(7): 1255-67 (Journal)
- Registered Authors
- Yang, Ruey-Bing (Ray)
- Keywords
- Bone µCT, Genetic animal models, Hedgehogs, Molecular pathways - development, osteoblast
- MeSH Terms
-
- Alkaline Phosphatase/metabolism
- Animals
- Cell Differentiation
- Cell Proliferation
- Chondrocytes/pathology
- Gene Targeting
- Growth Plate/metabolism
- HEK293 Cells
- Hedgehog Proteins/metabolism
- Humans
- Intercellular Signaling Peptides and Proteins/deficiency
- Intercellular Signaling Peptides and Proteins/metabolism*
- Ligands
- Mice
- Mice, Knockout
- NIH 3T3 Cells
- Osteoblasts/cytology
- Osteoblasts/metabolism
- Osteocalcin/metabolism
- Osteogenesis*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Signal Transduction
- Solubility
- PubMed
- 25639508 Full text @ J. Bone Miner. Res.
Citation
Lin, Y.C., Roffler, S.R., Yan, Y.T., Yang, R.B. (2015) Disruption of Scube2 impairs endochondral bone formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 30(7):1255-67.
Abstract
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 hedgehog ligands (Ihh and Dhh), and the developmental relevance of the SCUBE2-induced hedgehog 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 chondrocyte differentiation and proliferation as well as osteoblast differentiation of -/- bone-marrow mesenchymal stromal-cell cultures. Our data demonstrate that Scube2 plays a key regulatory role in Ihh-dependent endochondral bone formation. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping