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Neural EGFL like 1 as a potential pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug.

ABSTRACT: 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)1? 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 IL1?-stimulated inflammation and damage to articular cartilage in vivo. In particular, NELL-1 administration markedly reduced the symptoms of antalgic gait observed in IL1?-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.

SUBMITTER: Li C

PROVIDER: S-EPMC6938239 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Neural EGFL like 1 as a potential pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug.

Li Chenshuang C Zheng Zhong Z Ha Pin P Jiang Wenlu W Berthiaume Emily A EA Lee Seungjun S Mills Zane Z Pan Hsinchuan H Chen Eric C EC Jiang Jie J Culiat Cymbeline T CT Zhang Xinli X Ting Kang K Soo Chia C

Biomaterials 20191012

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<sup>+/6R</sup>) mice had accelerated and aggravated osteoarthritis (OA) progression with elevated inflammatory markers in both spontaneous primary OA and chemical-induced secondary OA models. I ...[more]

PMID: 31634652

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Project description:IntroductionEicosanoids are biological lipids that serve as both activators and suppressors of inflammation. Eicosanoid pathways are implicated in synovitis and joint destruction in inflammatory arthritis, yet they might also have a protective function, underscoring the need for a comprehensive understanding of how eicosanoid pathways might be imbalanced. Until recently, sensitive and scalable methods for detecting and quantifying a high number of eicosanoids have not been available.ObjectiveHere, we intend to describe a detailed eicosanoid profiling in patients with psoriatic arthritis (PsA) and evaluate correlations with parameters of disease activity.MethodsForty-one patients with PsA, all of whom satisfied the CASPAR classification criteria for PsA, were studied. Outcomes reflecting the activity of peripheral arthritis as well as skin psoriasis, Disease Activity Score (DAS)28, Clinical Disease Index (CDAI) and Body Surface Area (BSA) were assessed. Serum eicosanoids were determined by LC-MS, and the correlation between metabolite levels and disease scores was evaluated.ResultsSixty-six eicosanoids were identified by reverse-phase LC/MS. Certain eicosanoids species including several pro-inflammatory eicosanoids such as PGE2, HXB3 or 6,15-dk,dh,PGF1a correlated with joint disease score. Several eicosapentaenoic acid (EPA)-derived eicosanoids, which associate with anti-inflammatory properties, such as 11-HEPE, 12-HEPE and 15-HEPE, correlated with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) as well. Of interest, resolvin D1, a DHA-derived anti-inflammatory eicosanoid, was down-regulated in patients with high disease activity.ConclusionBoth pro- and anti-inflammatory eicosanoids were associated with joint disease score, potentially representing pathways of harm as well as benefit. Further studies are needed to determine whether these eicosanoid species might also play a role in the pathogenesis of joint inflammation in PsA.

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Neural EGFL like 1 as a potential pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug.

Publications

Neural EGFL like 1 as a potential pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug.

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