SummaryInterleukin-17 (IL-17 or IL-17A), a pleiotropic cytokine produced by T helper type 17 cells, is involved in the pathogenesis of various autoimmune and inflammatory disorders, including periodontitis. Although the ability of pro-inflammation in periodontitis has been widely investigated, the other biological functions of IL-17, including its role in bone remodelling and the underlying molecular mechanisms, have not been well clarified. In the present study, IL-17 could significantly enhance the expression of receptor activator for nuclear factor-jB ligand (RANKL) and inhibit the expression of osteoprotegerin (OPG) in human periodontal ligament cells, the two critical indicators for osteoclastogenesis, suggesting that IL-17 may play a destructive role in the pathogenesis of periodontal bone remodelling. Pharmaceutical signal inhibitors targeted at mitogen-activated protein kinases, Akt or nuclear factor-jB signals, inhibited IL-17-induced RANKL and OPG regulation. Notably, the enhancement of RANKL was significantly blocked by the inhibitors of c-Jun N-terminal kinase and nuclear factor-jB signals. The upstream signals were further investigated with the small interfering RNA. Both tumour necrosis factor receptor-associated factor 6 and TNF receptor associated factor (TRAF) family member-associated nuclear factor j-lightchain enhancer of activated B cells (NF-jB) activator (TANK)-binding kinase 1 were found to be the critical signal molecules for IL-17-dependent RANKL regulation in human periodontal ligament cells. These findings may provide comprehensive understanding of the role of IL-17 in the pathogenesis of periodontitis and might also provide a reasonable route for periodontitis therapy.

Autophagy is responsible for the lysosomal degradation of proteins, organelles, microorganisms and exogenous particles. Epidermis primarily consists of keratinocytes which functions as an extremely important barrier. Investigation on autophagy in keratinocytes has been continuously renewing, but is not so systematic due to the complexity of the autophagy machinery. Here we reviewed recent studies on the autophagy in keratinocyte with a focus on interplay between autophagy machinery and keratinocytes biology, and novel autophagy regulators identified in keratinocytes. In this review, we discussed the roles of autophagy in apoptosis, differentiation, immune response, survival and melanin metabolism, trying to reveal the possible involvement of autophagy in skin aging, skin disorders and skin color formation. Since autophagy routinely plays a double-edged sword role in various conditions, its functions in skin homeostasis and potential application as a therapeutic target for skin diseases remains to be clarified. Furthermore, more investigations are needed on optimizing designed strategies to inhibit or enhance autophagy for clinical efficacy.

A 3-D scaffold that simulates the microenvironment in vivo for regenerating cartilage is ideal. In this study, we combined silk fibroin and decellularized cartilage extracellular matrix by temperature gradient-guided thermal-induced phase separation to produce composite scaffolds (S/D). Resulting scaffolds had remarkable mechanical properties and biomimeticstructure, for a suitable substrate for attachment and proliferation of adipose-derived stem cells (ADSCs). Moreover, transforming growth factor β3 (TGF-β3) loaded on scaffolds showed a controlled release profile and enhanced the chondrogenic differentiation of ADSCs during the 28-day culture. The S/D scaffold itself can provide a sustained release system without the introduction of other controlled release media, which has potential for commercial and clinical applications. The results of toluidine blue, Safranin O, and immunohistochemical staining and analysis of collagen II expression showed maintenance of a chondrogenic phenotype in all scaffolds after 28-day culture. The most obvious phenomenon was with the addition of TGF-β3. S/D composite scaffolds with sequential delivery of TGF-β3 may mimic the regenerative microenvironment to enhance the chondrogenic differentiation of ADSCs in vitro.

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Background: Macrophage infiltration around lipotoxic tubular epithelial cells (TECs) is a hallmark of diabetic nephropathy (DN). However, how these two types of cells communicate remains obscure. We previously demonstrated that LRG1 was elevated in the process of kidney injury. Here, we demonstrated that macrophage-derived, LRG1-enriched extracellular vesicles (EVs) exacerbated DN. Methods: We induced an experimental T2DM mouse model with a HFD diet for four months. Renal primary epithelial cells and macrophage-derived EVs were isolated from T2D mice by differential ultracentrifugation. To investigate whether lipotoxic TEC-derived EV (EV e ) activate macrophages, mouse bone marrow-derived macrophages (BMDMs) were incubated with EV e . To investigate whether activated macrophage-derived EVs (EV m ) induce lipotoxic TEC apoptosis, EV m were cocultured with primary renal tubular epithelial cells. Subsequently, we evaluated the effect of LRG1 in EV e by investigating the apoptosis mechanism. Results: We demonstrated that incubation of primary TECs of DN or HK-2 mTECs with lysophosphatidyl choline (LPC) increased the release of EV e . Interestingly, TEC-derived EV e activated an inflammatory phenotype in macrophages and induced the release of macrophage-derived EV m . Furthermore, EV m could induce apoptosis in TECs injured by LPC. Importantly, we found that leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV e activated macrophages via a TGFβR1-dependent process and that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-enriched EV m induced apoptosis in injured TECs via a death receptor 5 (DR5)-dependent process. Conclusion: Our findings indicated a novel cell communication mechanism between tubular epithelial cells and macrophages in DN, which could be a potential therapeutic target.