Departmental Papers (Dental)
Date of this Version
Journal of Dental Research
Neural EGFL-like 1 (Nell-1) is a well-studied osteogenic factor that has comparable osteogenic potency with the Food and Drug Administration–approved bone morphogenic protein 2 (BMP-2). In this review, which aims to summarize the advanced Nell-1 research in the past 10 y, we start with the correlation of structural and functional relevance of the Nell-1 protein with the identification of a specific receptor of Nell-1, contactin-associated protein-like 4 (Cntnap4), for osteogenesis. The indispensable role of Nell-1 in normal craniofacial and appendicular skeletal development and growth was also defined by using the newly developed tissue-specific Nell-1 knockout mouse lines in addition to the existing transgenic mouse models. With the achievements on Nell-1’s osteogenic therapeutic evaluations from multiple preclinical animal models for local and systemic bone regeneration, the synergistic effect of Nell-1 with BMP-2 on osteogenesis, as well as the advantages of Nell-1 as an osteogenic protein with antiadipogenic, anti-inflammatory, and provascularized characteristics over BMP-2 in bone tissue engineering, is highlighted, which lays the groundwork for the clinical trial approval of Nell-1. At the molecular level, besides the mitogen-activated protein kinase (MAPK) signaling pathway, we emphasize the significant involvement of the Wnt/β-catenin pathway as well as the key regulatory molecules Runt-related transcription factor 2 (Runx2) in Nell-1-induced osteogenesis. In addition, the involvement of Nell-1 in chondrogenesis and its relevant pathologies have been revealed with the participation of the nuclear factor of activated T cells 1 (Nfatc1), Runx3, and Indian hedgehog (Ihh) signaling pathways, although the mechanistic insights of Nell-1’s osteochondrogenic property will be continuously evolving. With this perspective, we elucidate some emerging and novel functional properties of Nell-1 in oral-dental and neural tissues that will be the frontiers of future Nell-1 studies beyond the context of bone and cartilage. As such, the therapeutic potential of Nell-1 continues to evolve and grow with continuous pursuit. © International & American Associations for Dental Research 2019.
bone regeneration, bone remodeling, cartilage, chondrocytes, osteogenesis, osteoporosis, Animals, Calcium-Binding Proteins, Cell Differentiation, Chondrogenesis, Humans, Mice, Mice, Knockout, Osteogenesis, calcium binding protein, NELL1 protein, human, animal, bone development, cell differentiation, chondrogenesis, human, knockout mouse, mouse, physiology
Li, C., Zhang, X., Zheng, Z., Nguyen, A., Ting, K., & Soo, C. (2019). Nell-1 Is a Key Functional Modulator in Osteochondrogenesis and Beyond. Journal of Dental Research, 98 (13), 1458-1468. http://dx.doi.org/10.1177/0022034519882000
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. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.