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

Objective
The transcription factor Sox9, directly regulates the expression of the major proteoglycans and collagens comprising the cartilage extracellular matrix. The DNA-binding activity and cellular localization of Sox9 is controlled through posttranslational modifications including phosphorylation. Rho Kinase (ROCK) has profound effects on the actin cytoskeleton, which is instrumental in determining the chondrocyte phenotype and differentiation. How ROCK is mechanistically linked to altered chondrocyte gene expression remains unknown. The purpose of this study was to test for a direct interaction between ROCK and Sox9.

/pdf/rho-kinase-dependent-activation-of-sox9-in-chondrocytes-4x9bamuvdv.pdf

Rho kinase-dependent activation of SOX9 in chondrocytes.

Objective

WISP3 (Wnt-1–inducible secreted protein 3) is a member of the CCN (connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) family of connective tissue growth factors. WISP3 mutations have been linked to progressive pseudorheumatoid dysplasia (PPRD). The present study was conducted to investigate whether WISP3 is responsible for the expression of cartilage-specific molecules.



Methods

WISP3 expression in human cartilage was assessed by immunostaining with anti-WISP3 antibody. The effect of WISP3 on chondrocyte-specific gene regulation was determined by transfecting human chondrocyte lines C-28/I2 and T/C-28a2 with a WISP3 expression vector. Alterations in WISP3-mediated messenger RNA and protein expression of cartilage-specific molecules were assessed by reverse transcriptase–polymerase chain reaction and immunoblotting.



Results

Immunohistochemistry experiments demonstrated that WISP3 protein is expressed in the midzone chondrocytes of normal adult articular cartilage, in chondrocyte clusters of osteoarthritic cartilage, and in the zone of proliferating chondrocytes of fetal growth cartilage. Human chondrocyte lines C-28/I2 and T/C-28a2 transfected with a WISP3 expression vector produced increased amounts of the cartilage-specific matrix molecules type II collagen and aggrecan, in part via activation of the sex-determining region Y–type high mobility group box (SOX) family of transcription factors. In contrast, a mutant WISP3, previously found to be associated with PPRD, had impaired effects on cartilage-specific gene expression.



Conclusion

Our experimental results suggest that WISP3 supports cartilage integrity by regulating the expression of type II collagen and aggrecan, and mutations linked with PPRD can compromise this function and produce cartilage loss.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.20005

WISP3-dependent regulation of type II collagen and aggrecan production in chondrocytes.

The occurrence of chondrocyte apoptosis may be cri­tical in determining the extent of a lesion and sub­sequent repair after mechanical injury to articular cartilage. Agents that prevent apoptosis and increase chondrocyte survival may prove beneficial in the treatment of these ­lesions. This set of experiments was designed to determine the efficacy of some known apoptosis inhibitors in preventing chon­drocyte apoptosis after mechanical injury.

In the first set of experiments, thirty full-thickness cartilage explants, 5 mm in diameter, were harvested from the weight-bearing regions of the medial femoral condyle of three fresh bovine joints with use of a dermal punch. Explants were cultured for forty-eight hours in Dulbecco modified Eagle medium supplemented with 10% fetal bovine serum. Explants were divided into three groups: control, loaded, and loaded + CI. The loaded group was subjected to a radially unconfined single static load of 23 MPa for 500 msec and recultured in fresh media for forty-eight hours postinjury. The loaded + CI group underwent the same loading, but the specimens were cultured in fresh media containing 100 mM of the caspase ­inhibitor z-VAD.fmk. The control group did not undergo loading. In a second set of experiments, forty-eight bovine cartilage explants were divided into four groups: control, loaded, loaded + D, and loaded + I. The loaded, loaded …

Prevention of Chondrocyte Apoptosis

Recent studies suggest that histone deacetylase (HDAC) inhibitors may therapeutically prevent cartilage degradation in osteoarthritis (OA). Matrix metalloproteinase-13 (MMP-13) plays an important role in the pathogenesis of this disease and in the present study we investigated the correlation between HDACs and MMP-13. Comparing the expression of different HDACs in cartilage from OA patients and healthy donors, HDAC7 showed a significant elevation in cartilage from OA patients. High level of HDAC7 expression in OA cartilage was also confirmed by immunohistochemistry. Knockdown of HDAC7 by small interference RNA (siRNA) in SW1353 human chondrosarcoma cells strongly suppressed interleukin (IL)-1-dependent and independent induction of MMP-13 gene expression. In conclusion, elevated HDAC7 expression in human OA may contribute to cartilage degradation via promoting MMP-13 gene expression, suggesting the critical role of MMP-13 in OA pathogenesis.

Martin Lotz

Papers

Rho kinase-dependent activation of SOX9 in chondrocytes.

WISP3-dependent regulation of type II collagen and aggrecan production in chondrocytes.

Prevention of Chondrocyte Apoptosis

Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis

Biomechanical regulation of matrix metalloproteinase-9 in cultured chondrocytes.