Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types. The principal routine function of IL-10 appears to be to limit and ultimately terminate inflammatory responses. In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses. This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease.

Interleukin-10 and the interleukin-10 receptor.

Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

3D bioprinting of tissues and organs

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

CD4+ T cells, upon activation and expansion, develop into different T helper cell subsets with different cytokine profiles and distinct effector functions. Until recently, T cells were divided into Th1 or Th2 cells, depending on the cytokines they produce. A third subset of IL-17-producing effector T helper cells, called Th17 cells, has now been discovered and characterized. Here, we summarize the current information on the differentiation and effector functions of the Th17 lineage. Th17 cells produce IL-17, IL-17F, and IL-22, thereby inducing a massive tissue reaction owing to the broad distribution of the IL-17 and IL-22 receptors. Th17 cells also secrete IL-21 to communicate with the cells of the immune system. The differentiation factors (TGF-β plus IL-6 or IL-21), the growth and stabilization factor (IL-23), and the transcription factors (STAT3, RORγt, and RORα) involved in the development of Th17 cells have just been identified. The participation of TGF-β in the differentiation of Th17 cells places ...

IL-17 and Th17 Cells.

Freedom of design, mass customisation, waste minimisation and the ability to manufacture complex structures, as well as fast prototyping, are the main benefits of additive manufacturing (AM) or 3D printing. A comprehensive review of the main 3D printing methods, materials and their development in trending applications was carried out. In particular, the revolutionary applications of AM in biomedical, aerospace, buildings and protective structures were discussed. The current state of materials development, including metal alloys, polymer composites, ceramics and concrete, was presented. In addition, this paper discussed the main processing challenges with void formation, anisotropic behaviour, the limitation of computer design and layer-by-layer appearance. Overall, this paper gives an overview of 3D printing, including a survey on its benefits and drawbacks as a benchmark for future research and development.

Additive manufacturing (3D printing): A review of materials, methods, applications and challenges

Comment on ”Crystallographic and theoretical study of the atypical distorted octahedral geometry of the metal chromophore of zinc(II) bis((1R,2R)-1,2-diaminocyclohexane) dinitrate”

054 extracellular sulfatases support cartilage homeostasis by regulating bmp and fgf signaling pathways

Induction of Mesenchymal Stem Cell Differentiation to a Meniscus Cell Phenotype by a Combination of Mohawk Transcription Factor and TGF-ß For Meniscus Repair and Regeneration

Background: In Osteoarthritis (OA), defects in macroautophagy (autophagy) are evident and precede joint damage Indeed, pharmacological activation of autophagy protects against joint damage Objectives: Therefore, identifying hallmarks associated with specific autophagy subtypes could shed light to fundamental mechanisms of joint disease Methods: A comparative analysis of 35 autophagy genes was performed from blood from the Prospective OA Cohort of A Coruna (PROCOAC) Non-OA subjects (Age:61,44±1,16 years; BMI:25,25±0,52; Females, n=18) and Knee OA subjects (Age:65,50±1,05 years; BMI:29,55±0,67; Females, n=18, OA grade III-IV) were profiled using an autophagy gene expression array by SYBR green qPCR Confirmatory studies were performed in blood from Non-OA subjects (Age:60,13±1,12 years; BMI:24,85±0,59; Females; n=30) and Knee-OA subjects (Age:68,4±1,11 years; BMI:29,65±0,55; Females; n=30, OA grade III-IV) by Taqman qPCR The candidate gene was evaluated in human knee joint tissues (cartilage, meniscus, ligaments, synovium) with different KL grades (Age: KL0=28,3±4,50; KL2=77±6,08; KL4=62,3±3,05, n=3) and in both spontaneous aging (2, 6, 12, 18, and 30 months old, n=3) and surgically-induced OA (10 weeks after surgery, n=4) in mice by IHC The functional consequences were studied in T/C28a2 and primary human OA chondrocytes Autophagy, FOXO, Chaperone-mediated autophagy (CMA), inflammation, and cellular senescence were analyzing by gene and protein expression Moreover, oxidative stress and cell death were evaluated by FACS The contribution of CMA to chondrocyte homeostasis was evaluated by studying the capacity of CMA to restore proteostasis upon autophagy deficiency by siATG5 Results: 15 autophagy-related genes were significantly downregulated in blood from knee OA patients compared to non-OA patients No significant upregulation was found for any studied gene, although a trend towards upregulation was found in genes involved in the mTOR pathway Four key autophagy-related genes, including ATG16L2, ATG12, ATG4B and MAP1LC3B were found downregulated in knee OA patients Interestingly, HSP90AA1 and HSPA8, CMA markers involved in stress response and protein folding, were downregulated Confirmatory studies showed a significant downregulation of MAP1LC3B and HSP90AA1 in blood from knee OA patients Remarkably, HSP90A was found reduced in femoral cartilage (medial and lateral), meniscus and ACL Moreover, this reduction was higher in medial cartilage compared to lateral cartilage and meniscus, while in synovial membrane, HSP90A expression was found increased This expression signature was dependent on OA grade severity In addition, we observed a decrease of HSP90A with aging and OA in mice The functional consequences of HSP90AA1 gene silencing are related to an increase in NFκB, MMP13, and p16 expression Interestingly, LAMP2A, a key CMA mediator, HSPA8, MAP1LC3B and FoxO1 expression were upregulated in chondrocytes with HSP90AA1 deficiency, which might indicate an early response to maintain homeostasis On the other hand, LAMP2A protein is decreased upon HSP90AA1 deficiency, while LC3II and p62 were increased, indicating a failure in the autophagy flux that leads to impaired lysosomal degradation Moreover, p21, p16 and prbS6 were increased upon HSP90AA1 deficiency, besides increasing mitochondrial ROS production and apoptosis ATG5 silencing blocks autophagy by reducing LC3II and increasing prbs6, p62, p16 and p21 Interestingly, LAMP2A and HSP90A were found increased, indicating a possible compensative activation of CMA in response to autophagy defects These results support that HSP90A has an important role in chondrocyte homeostasis by participating in the cross-talk between CMA and autophagy Conclusion: Taking together, we identified HSP90A, a CMA regulator, as critical in chondrocyte homeostasis These disease mechanisms are relevant in OA and constitute hallmarks potentially useful to prevent OA progression References: [1]Carames B, et al Arthritis Rheum 2010, 2015; [2]Carames B, et al Ann Rheum Dis 2012 Disclosure of Interests: None declared

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Pos0375 chaperone-mediated autophagy is a hallmark of joint disease in osteoarthritic patients

Objective: Osteoarthritis (OA) is a multifactorial disease with etiological heterogeneity. The objective of this study was to classify OA subgroups by generating metabolic phenotypes of OA from human synovial fluid. Design: Post mortem synovial fluids (n=75) were analyzed by high performance-liquid chromatography mass spectrometry (HPLC-MS) to measure changes in the global metabolome. Comparisons of healthy (grade 0), early OA (grades I-II), and late OA (grades III-IV) donor populations were considered to reveal phenotypes throughout disease progression. Results: Global metabolomic profiles in synovial fluid were distinct between healthy, early OA, and late OA donors. Pathways differentially activated among these groups included structural deterioration, glycerophospholipid metabolism, inflammation, central energy metabolism, oxidative stress, and vitamin metabolism. Within disease states (early and late OA), subgroups of donors revealed distinct phenotypes. Phenotypes of OA exhibited increased inflammation (early and late OA), oxidative stress (late OA), or structural deterioration (early and late OA) in the synovial fluid. Conclusion: These results revealed distinct metabolic phenotypes of OA in human synovial fluid, provide insight into pathogenesis, represent novel biomarkers and assist in developing personalized interventions for subgroups of OA patients.

https://www.biorxiv.org/content/biorxiv/early/2018/09/07/395020.full.pdf

Martin Lotz

Papers

Comment on ”Crystallographic and theoretical study of the atypical distorted octahedral geometry of the metal chromophore of zinc(II) bis((1R,2R)-1,2-diaminocyclohexane) dinitrate”

054 extracellular sulfatases support cartilage homeostasis by regulating bmp and fgf signaling pathways

Induction of Mesenchymal Stem Cell Differentiation to a Meniscus Cell Phenotype by a Combination of Mohawk Transcription Factor and TGF-ß For Meniscus Repair and Regeneration

Pos0375 chaperone-mediated autophagy is a hallmark of joint disease in osteoarthritic patients

Characterization of osteoarthritis phenotypes by global metabolomic profiling of human synovial fluid