NELL-1 expression in tumors of cartilage

Shen, Jia; LaChaud, Gregory; Shrestha, Swati; Asatrian, Greg; Zhang, Xinli; Dry, Sarah M.; Ting, Kang; James, Aaron W.

doi:10.1016/j.jor.2015.10.001

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…22,23 Although NELL-1 is expressed among many skeletal tumors, its expression does not correlate with benign versus malignant tumor types. 24,25 Finally, NELL-1 has an excellent safety profile. Mice with constitutive Nell-1 overexpression have a normal lifespan without increased development of tumors.…”

Section: Discussionmentioning

confidence: 99%

Age dependent effects of NELL-1 isoforms on bone marrow stromal cells

Meyers

Sun

Chang

et al. 2019

Journal of Orthopaedics

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NELL-1 is an osteogenic protein first discovered to control ossification of the cranium. NELL-1 exists in at least two isoforms. The full-length NELL-1 contains 810 amino acid (aa) (NELL-1810), the N-terminal-truncated NELL-1 isoform contains 570 aa (NELL-1570). The differences in cellular effects between NELL-1 isoforms are not well understood. Methods: Here, BMSC were derived from adult or aged mice, followed by overexpression of NELL-1810 or NELL-1570. Cell morphology, proliferation, and gene expression were examined. Results/Conclusions: Overall, the proliferative effect of NELL-1570 was age dependent, showing prominent induction in adult but not aged mice.

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Section: Discussionmentioning

confidence: 99%

Age dependent effects of NELL-1 isoforms on bone marrow stromal cells

Meyers

Sun

Chang

et al. 2019

Journal of Orthopaedics

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“…In contrast, a relative reduction in Nell-1 staining was observed in osteosarcoma with large variation among tumors (Shen, LaChaud, Khadarian, et al 2015). In addition, Nell-1 expression did not significantly vary by the type and grade of the cartilage-forming tumors (Shen, LaChaud, Shrestha, et al 2015). These associations of Nell-1 expression with tumor tissues make the effects of Nell-1 in tumorigenesis inconclusive.…”

Section: Extensive Preclinical Experimentations In Nell-1’s Therapeutmentioning

confidence: 95%

Nell-1 Is a Key Functional Modulator in Osteochondrogenesis and Beyond

Zhang

Zheng

et al. 2019

J Dent Res

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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.

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“…NELL-1 has documented tumor-suppression properties and its expression is lost in several carcinomas (32,33). Recently, we documented high expression of NELL-1 among several bone-and cartilage-forming tumors, but its expression does not correlate with benign and malignant tumor types (34,35). Finally, NELL-1 has an excellent safety profile.…”

Section: Cd31mentioning

confidence: 96%