Neural EGFL-Like 1 Is a Downstream Regulator of Runt-Related Transcription Factor 2 in Chondrogenic Differentiation and Maturation
Penn collection
Degree type
Discipline
Subject
Calcium-Binding Proteins
Cartilage
Cell Differentiation
Cell Proliferation
Chondrocytes
Chondrogenesis
Core Binding Factor Alpha 1 Subunit
Femur
Glycoproteins
Hindlimb
Mice
Inbred C57BL
Regeneration
neural egfl like 1
scleroprotein
transcription factor RUNX2
unclassified drug
calcium binding protein
glycoprotein
Nell1 protein
mouse
Runx2 protein
mouse
transcription factor RUNX2
animal cell
animal tissue
Article
cartilage
cell differentiation
cell lineage
cell maturation
chondrocyte
chondrogenesis
controlled study
DNA binding
embryo
ex vivo study
in vitro study
mouse
newborn
nonhuman
nuclear import
osteoblast
priority journal
protein expression
tissue regeneration
animal
C57BL mouse
cell differentiation
cell proliferation
chondrogenesis
embryology
femur
growth
development and aging
hindlimb
physiology
regeneration
Dental Materials
Dentistry
Orthodontics and Orthodontology
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Abstract
Recent studies indicate that neural EGFL-like 1 (Nell-1), a secretive extracellular matrix molecule, is involved in chondrogenic differentiation. Herein, we demonstrated that Nell-1 serves as a key downstream target of runt-related transcription factor 2 (Runx2), a central regulator of chondrogenesis. Unlike in osteoblast lineage cells where Nell-1 and Runx2 demonstrate mutual regulation, further studies in chondrocytes revealed that Runx2 tightly regulates the expression of Nell-1; however, Nell-1 does not alter the expression of Runx2. More important, Nell-1 administration partially restored Runx2 deficiency–induced impairment of chondrocyte differentiation and maturation in vitro, ex vivo, and in vivo. Mechanistically, although the expression of Nell-1 is highly reliant on Runx2, the prochondrogenic function of Nell-1 persisted in Runx2−/− scenarios. The biopotency of Nell-1 is independent of the nuclear import and DNA binding functions of Runx2 during chondrogenesis. Nell-1 is a key functional mediator of chondrogenesis, thus opening up new possibilities for the application of Nell-1 in cartilage regeneration. © 2017 American Society for Investigative Pathology