Fructose‐Derived Levan Nanoparticles Protect Against Osteoarthritis by Directly Blocking CD44 Activation

Abstract

Although the development of several inflammatory diseases can be initiated in response to CD44 receptor signaling dysregulation, anti‐CD44 antibody therapy has been discontinued in clinical trials owing to its severe adverse effects. Moreover, biocompatible materials that block CD44 are unknown. Here, self‐assembled levan nanoparticles (LevNPs) through simple nanoprecipitation without chemical conjugation of biocompatible levan are developed. LevNPs are prepared through a simple nanoprecipitation without chemical conjugation; this results in particles with a consistently dispersed hydrodynamic diameter of approximately 230 nm. The physicochemical properties of LevNP are well‐maintained even after long‐term storage in a physiological buffer, suggesting that LevNPs are stable and useful for various biomedical applications. A protein array and an in silico LevNP‐CD44 interaction assay reveal that LevNPs specifically bind to CD44. Importantly, CD44 is highly expressed in the cartilage of patients with osteoarthritis (OA). LevNPs showed no cytotoxicity and reduced catabolic factor expression in an OA mimic in vitro. Furthermore, intra‐articular injection of LevNPs exhibited long‐term retention ability in the knee joint and protection against posttraumatic OA cartilage destruction in mice with medial meniscus destabilization–induced OA. These results show that LevNPs are biocompatible and exhibit potential as a nanotherapeutic for protecting against OA pathogenesis by directly blocking CD44.

Blockade of Activin Receptor IIB Protects Arthritis Pathogenesis by Non‐Amplification of Activin A‐ACVR2B‐NOX4 Axis Pathway

“…Chondrocytes were cultured for 2 d and infected with adenovirus for 2 h at the indicated multiplicity of infection (MOI). [ 69 ] The postnatal chondrocytes from activin A Tg and WT littermates were grown for 24 h in serum‐free medium to 90% confluency. The supernatant medium was concentrated using Microsep Advance with 10K Omega (PALL, NY, USA) and treated as indicated.…”

Mechanisms of vascular invasion after cartilage injury and potential engineering cartilage treatment strategies

“…Cho et al. injected mice with OA with a nanoparticle that directly blocks CD44 in the articular cavity and displayed protective effects against damaged cartilage 79 …”

WGA-M001, a Mixture of Total Extracts of Tagetes erecta and Ocimum basilicum, Synergistically Alleviates Cartilage Destruction by Inhibiting ERK and NF-κB Signaling

“…To verify the in vivo functions of WGA-M001, T. erecta, and O. basilicum, we destabilized the medial meniscus (DMM)-induced OA according to the schedule shown in Figure S2. The DMM-induced OA mouse model is a highly representative in vivo model for OA [33,34]. WGA-M001, T. erecta, or O. basilicum was orally administered to mice with DMM-induced OA.…”

“…IL-6 production was quantified using a mouse IL-6 ELISA kit (Koma Biotech, Seoul, South Korea), according to the manufacturer's instructions. Absorbance for IL-6 was measured at 450 nm using a microplate reader (VICTOR X3; PerkinElmer, Waltham, USA) [33,34,59].…”

“…For the experimental OA model, 10-week-old male C57BL/6 mice underwent DMM surgery using a previously described protocol [33,34]. Each experiment was conducted independently at least five times.…”