Departmental Papers (Dental)

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Journal Article

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Article number 119541




Arthritis, an inflammatory condition that causes pain and cartilage destruction in joints, affects over 54.4 million people in the US alone. Here, for the first time, we demonstrated the emerging role of neural EGFL like 1 (NELL-1) in arthritis pathogenesis by showing that Nell-1-haploinsufficient (Nell-1+/6R) mice had accelerated and aggravated osteoarthritis (OA) progression with elevated inflammatory markers in both spontaneous primary OA and chemical-induced secondary OA models. In the chemical-induced OA model, intra-articular injection of interleukin (IL)1β induced more severe inflammation and cartilage degradation in the knee joints of Nell-1+/6R mice than in wildtype animals. Mechanistically, in addition to its pro-chondrogenic potency, NELL-1 also effectively suppressed the expression of inflammatory cytokines and their downstream cartilage catabolic enzymes by upregulating runt-related transcription factor (RUNX)1 in mouse and human articular cartilage chondrocytes. Notably, NELL-1 significantly reduced IL1β-stimulated inflammation and damage to articular cartilage in vivo. In particular, NELL-1 administration markedly reduced the symptoms of antalgic gait observed in IL1β-challenged Nell-1+/6R mice. Therefore, NELL-1 is a promising pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug (DMOAD) candidate for preventing and suppressing arthritis-related cartilage damage. © 2019 Elsevier Ltd


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.


Cartilage damage, Disease-modifying osteoarthritis drug (DMOAD), Inflammation, Neural EGFL like 1 (NELL-1), Osteoarthritis, Runt-related transcription factor 1 (RUNX1), Animals, Anti-Inflammatory Agents, Cartilage, Articular, Chondrocytes, Chondrogenesis, Interleukin-1beta, Mice, Osteoarthritis, Pharmaceutical Preparations, Cartilage, Diseases, Mammals, Pathology, Transcription, Transcription factors, disease modifying antirheumatic drug, interleukin 1beta, membrane protein, neural EGFL like 1, transcription factor RUNX1, unclassified drug, antiinflammatory agent, drug, interleukin 1beta, Cartilage damage, Inflammation, Neural EGFL like 1 (NELL-1), Osteoarthritis, Runt-related transcription factor 1 (RUNX1), animal experiment, animal model, animal tissue, Article, controlled study, drug efficacy, female, knee osteoarthritis, molecular pathology, mouse, nonhuman, outcome assessment, predictive value, priority journal, protein function, single nucleotide polymorphism, animal, articular cartilage, chondrocyte, chondrogenesis, osteoarthritis, Joints (anatomy)



Date Posted: 10 February 2023

This document has been peer reviewed.