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Notch signaling through the Jagged‐1 ligand regulates mesenchymal progenitor differentiation and tissue regeneration
Author(s) -
Hankenson Kurt D
Publication year - 2012
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.26.1_supplement.198.6
Subject(s) - notch signaling pathway , intramembranous ossification , microbiology and biotechnology , mesenchymal stem cell , progenitor cell , regeneration (biology) , osteoblast , endochondral ossification , hes3 signaling axis , cellular differentiation , chemistry , biology , stem cell , signal transduction , anatomy , cartilage , genetics , gene , in vitro
Notch signaling regulates stem cell differentiation and expansion and influences formation and maintenance of bone. Loss‐of‐function mutations in the Notch ligand Jagged‐1, which are associated with Allagille's Syndrome, result in decreased bone mass. Notch signaling is also implicated in modulating the regeneration of a variety of non‐mineralized tissues. We hypothesize that Notch signaling through Jagged‐1 is crucial for bone regeneration through the regulation of mesenchymal progenitor cell (mesenchymal stem cell – MSC) expansion and differentiation. Canonical notch signaling through Jagged‐1 has pleiotropic, variable effects on MSC lineage progression and proliferation. Jagged‐1 activity is influenced by bone morphogenetic signaling and modulatory proteins of the thrombospondin family. Blocking canonical Notch signaling in mice results in age‐associated bone loss, while mice with conditional deletion of Jagged‐1 show related alterations in bone mass. Notch signaling is up‐regulated during both intramembranous and endochondral bone regeneration and corresponds to increases in expression of Jagged‐1. Jagged‐1 can be coupled to biodegradable biomaterials and induces increased osteoblast differentiation of MSC. Jagged‐1 coupled biomaterial can then be implanted at the site of bone defects and used to modulate bone regeneration. This work was supported by the DOD and NIH.