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Journal article
Primary cilia control cell alignment and patterning in bone development via ceramide-PKC zeta-beta-catenin signaling
Communications biology, v 3(1), pp 45-45
27 Jan 2020
PMCID: PMC6985158
PMID: 31988398
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Lim et al. find that osteoblast-specific deletion of IFT20 impairs osteoblast/osteocyte cell alignment and reduces bone mass. Their results further show that the mechanism underlying IFT20-associated bone ciliopathies involves defects in cell polarity caused by deficient Ceramide-PKC zeta recruitment to cilia and reduced beta-catenin signaling, which interferes with bone development.
Intraflagellar transport (IFT) proteins are essential for cilia assembly and function. IFT protein mutations lead to ciliopathies, which manifest as variable skeletal abnormalities. However, how IFT proteins regulate cell alignment during bone development is unknown. Here, we show that the deletion of IFT20 in osteoblast lineage using Osterix-Cre and inducible type I Collagen-CreERT cause a compromised cell alignment and a reduced bone mass. This finding was validated by the disorganized collagen fibrils and decreased bone strength and stiffness in IFT20-deficient femurs. IFT20 maintains cilia and cell alignment in osteoblasts, as the concentric organization of three-dimensional spheroids was disrupted by IFT20 deletion. Mechanistically, IFT20 interacts with the ceramide-PKC zeta complex to promote PKC zeta phosphorylation in cilia and induce the apical localization of beta-catenin in osteoblasts, both of which were disrupted in the absence of IFT20. These results reveal that IFT20 regulates polarity and cell alignment via ceramide-pPKC zeta-beta-catenin signaling during bone development.
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Details
- Title
- Primary cilia control cell alignment and patterning in bone development via ceramide-PKC zeta-beta-catenin signaling
- Creators
- Jormay Lim - University of PennsylvaniaXinhua Li - University of PennsylvaniaXue Yuan - University at Buffalo, State University of New YorkShuting Yang - Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USALin Han - Drexel Univ, Dept Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USAShuying Yang - University of Pennsylvania
- Publication Details
- Communications biology, v 3(1), pp 45-45
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- DE023105; AR061052 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000510948400001
- Scopus ID
- 2-s2.0-85078333176
- Other Identifier
- 991019169596104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biology