Departmental Papers (Dental)
Neural EGFL-Like 1 Is a Downstream Regulator of Runt-Related Transcription Factor 2 in Chondrogenic Differentiation and Maturation
Date of this Version
American Journal of Pathology
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
Animals, 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
Li, C., Jiang, J., Zheng, Z., Lee, K. S., Zhou, Y., Chen, E., Culiat, C. T., Qiao, Y., Chen, X., Ting, K., Zhang, X., & Soo, C. (2017). Neural EGFL-Like 1 Is a Downstream Regulator of Runt-Related Transcription Factor 2 in Chondrogenic Differentiation and Maturation. American Journal of Pathology, 187 (5), 963-972. http://dx.doi.org/10.1016/j.ajpath.2016.12.026
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California and the Peking University, School and Hospital of Stomatology. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.