Link N suppresses interleukin-1ß-induced biological effects on human osteoarthritic cartilage.

Osteoarthritis (OA) is a disease of diarthrodial joints associated with extracellular matrix proteolytic degradation under inflammatory conditions, pain and disability. Currently, there is no therapy to prevent, reverse or modulate the disease course. The present study aimed at evaluating the regenerative potential of Link N (LN) in human OA cartilage in an inflammatory milieu and determining if LN could affect pain-related behaviour in a knee OA mouse injury model. Osteo-chondro OA explants and OA chondrocytes were treated with LN in the presence of interleukin-1ß (IL-1ß) to simulate an osteoarthritic environment. Quantitative von Frey polymerase chain reaction and Western blotting were performed to determine the effect of LN on matrix protein synthesis, catabolic enzymes, cytokines and nerve growth factor expression. Partial medial meniscectomy (PMM) was performed on the knee of C57BL/6 mice and, 12 weeks post-surgery, mice were given a 5 µg intra-articular injection of LN or phosphate-buffered saline. A von Frey test was conducted over 24 h to measure the mechanical allodynia in the hind paw. LN modulated proteoglycan and collagen synthesis in human OA cartilage through inhibition of IL-1ß-induced biological effects. LN also supressed IL-1ß-induced upregulation of cartilage-degrading enzymes and inflammatory molecules in OA chondrocytes. Upon investigation of the canonical signalling pathways IL-1ß and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), LN resulted to significantly inhibit NF-κB activation in a dose-dependent manner. In addition, LN suppressed mechanical allodynia in an OA PMM mouse model. Results supported the concept that LN administration could provide therapeutic potential in OA.

Gut Microbiota in Vascular Disease: Therapeutic Target?

BACKGROUND: Gut microbiota is increasingly recognized as a powerful regulator of host physiology. Most of its effects are mediated through metabolites acting as energy sources, signaling receptor ligands and substrates for host enzymes. Owing to the meta-stability and high amenability of the gut microbiota to modification by diet and environment predicting specific gut microbes or its metabolites responsible for different host metabolic states is often confounded. METHODS: The Pubmed was searched for research articles on gut microbiota and cardiovascular disease. RESULTS: The searched articles reported a direct role of gut microbes in cardiovascular disorders (CVD). The interaction among gut microbial metabolism (through breakdown of certain dietary nutrients like choline), host immune system and lipid metabolism generate conditions that promote atherosclerosis development. Importantly, components of this interactive system can be explored to identify points of intervention in the path of disease development. Based on this strategies targeting gut microbial composition and activity are being explored as therapies against CVD. Use of archaebiotics and 3,3-dimethyl- 1-butanol aiming to reduce TMA (trimethylamine) conversion to TMAO (trimethylamine-N-oxide) and high fibre diets to reduce TMA precursors while simultaneously selecting for beneficial gut bacteria are attractive anti-atherogenic approaches. CONCLUSION: Success of these approaches in humans however, requires extensive research.