Neural EGFL Like 1 as a Potential Pro-Chondrogenic, Anti-Inflammatory Dual-Functional Disease-Modifying Osteoarthritis Drug

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 Lt

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

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

Using an Engineered Galvanic Redox System to Generate Positive Surface Potentials that Promote Osteogenic Functions

Successful osseointegration of orthopaedic and orthodontic implants is dependent on a competition between osteogenesis and bacterial contamination on the implant–tissue interface. Previously, by taking advantage of the highly interactive capabilities of silver nanoparticles (AgNPs), we effectively introduced an antimicrobial effect to metal implant materials using an AgNP/poly­(dl-lactic-<i>co</i>-glycolic acid) (PLGA) coating. Although electrical forces have been shown to promote osteogenesis, creating practical materials and devices capable of harnessing these forces to induce bone regeneration remains challenging. Here, we applied galvanic reduction–oxidation (redox) principles to engineer a nanoscale galvanic redox system between AgNPs and 316L stainless steel alloy (316L-SA). Characterized by scanning electron microscopy , energy-dispersive X-ray spectroscopy, atomic force microscopy, Kelvin probe force microscopy, and contact angle measurement, the surface properties of the yield AgNP/PLGA-coated 316L-SA (SNPSA) material presented a significantly increased positive surface potential, hydrophilicity, surface fractional polarity, and surface electron accepting/donating index. Importantly, in addition to its bactericidal property, SNPSA’s surface demonstrated a novel osteogenic bioactivity by promoting peri-implant bone growth. This is the first report describing the conversion of a normally deleterious galvanic redox reaction into a biologically beneficial function on a biomedical metal material. Overall, this study details an innovative strategy to design multifunctional biomaterials using a controlled galvanic redox reaction, which has broad applications in material development and clinical practice

Using an Engineered Galvanic Redox System to Generate Positive Surface Potentials that Promote Osteogenic Functions

Successful osseointegration of orthopaedic and orthodontic implants is dependent on a competition between osteogenesis and bacterial contamination on the implant–tissue interface. Previously, by taking advantage of the highly interactive capabilities of silver nanoparticles (AgNPs), we effectively introduced an antimicrobial effect to metal implant materials using an AgNP/poly­(dl-lactic-<i>co</i>-glycolic acid) (PLGA) coating. Although electrical forces have been shown to promote osteogenesis, creating practical materials and devices capable of harnessing these forces to induce bone regeneration remains challenging. Here, we applied galvanic reduction–oxidation (redox) principles to engineer a nanoscale galvanic redox system between AgNPs and 316L stainless steel alloy (316L-SA). Characterized by scanning electron microscopy , energy-dispersive X-ray spectroscopy, atomic force microscopy, Kelvin probe force microscopy, and contact angle measurement, the surface properties of the yield AgNP/PLGA-coated 316L-SA (SNPSA) material presented a significantly increased positive surface potential, hydrophilicity, surface fractional polarity, and surface electron accepting/donating index. Importantly, in addition to its bactericidal property, SNPSA’s surface demonstrated a novel osteogenic bioactivity by promoting peri-implant bone growth. This is the first report describing the conversion of a normally deleterious galvanic redox reaction into a biologically beneficial function on a biomedical metal material. Overall, this study details an innovative strategy to design multifunctional biomaterials using a controlled galvanic redox reaction, which has broad applications in material development and clinical practice