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BackgroundThe previous studies indicated that CrmA could ameliorate the interleukin-1β induced osteoarthritis. In this study, we investigated the controlled-released cytokine response modifier A (CrmA) from hyaluronic acid (HA)-chitosan (CS) microspheres to improve interleukin-1β (IL-1β)-stimulated dedifferentiation of chondrocytes.MethodsA rat model of osteoarthritis (OA) in vitro was established using 10 ng/ml IL-1β as modulating and chondrocytes inducing agent. HA-CS-CrmA microspheres were added to the medium after IL-1β was co-cultured with freshly isolated rat chondrocytes for 48 hours. The chondrocytes viability and glycosaminoglycan (GAG) content were determined. The level of CrmA secreted was detected by Enzyme-Linked Immunosorbent Assay (ELISA). The protein levels of type II collagen, aggrecan, collagen I and IL-1β were detected using western blotting analyses.ResultsThe CrmA release kinetics were characterized by an initial burst release, which was reduced to a linear release over ten days. The production of GAG and the expression of type II collagen, aggrecan significantly increased compared with the control group, while the expression of collagen I and IL-1β decreased.ConclusionsThis study demonstrated that HA-CS microspheres containing CrmA could attenuate the degeneration of articular cartilage by maintaining the phenotype of chondrocytes during culture expansion. The suppression of inflammatory cytokines activity within the joint might be one important mechanism of the action of the microspheres in the treatment of OA.

Background Angiogenesis is required in many physiological conditions, including bone regeneration, wound healing, and tissue regeneration. Mesenchymal stem cells-derived extracellular matrix (MSCs-ECM) could guide intricate cellular and tissue processes such as homeostasis, healing and regeneration. Methods The purpose of this study is to explore the effect and mechanism of ECM derived from decellularized Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) on endothelial cell viability and angiogenesis. The human umbilical vein endothelial cells (HUVECs) were pretreated with WJ-MSCs ECM for 2d/7d/14d, respectively. After pretreatment, the angiogenesis ability of HUVECs was detected. Results In this study, we found for the first time that WJ-MSCs ECM could improve the angiogenesis ability of HUVECs with a time-dependent manner in vitro. Mechanically, WJ-MSCs ECM activated the focal adhesion kinase (FAK)/P38 signaling pathway via integrin αVβ3, which further promoted the expression of the cellular (c)-Myc. Further, c-Myc increased histone acetylation levels of the vascular endothelial growth factor (VEGF) promoter by recruiting P300, which ultimately promoting VEGF expression. Conclusions ECM derived from Wharton’s Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF. This study is expected to provide a new approach to promote angiogenesis in bone and tissue regeneration.

The aim of the study was to determine whether the controlled release of interleukin (IL)-1Ra from chitosan (CS) microspheres inhibits the IL-1β-stimulated production of matrix metalloproteinases (MMPs) in chondrocytes. The CS-IL-1Ra microspheres were fabricated by an emulsification method using sodium tripolyphosphate as a crosslinker, and the controlled release of IL-1Ra was determined using an enzyme-linked immunosorbent assay. IL-1β was added to normal rat chondrocytes to stimulate MMP production. The chondrocytes were incubated with CS-IL-1Ra microspheres to assess its effects on IL-1β-induced MMP expression. Chondrocyte proliferation and glycosaminoglycan (GAG) content were also determined. The mRNA expression and protein levels of IL-1β, MMP-1, MMP-3 and MMP-13 were detected using reverse transcription-polymerase chain reaction and western blotting analyses, respectively. The IL-1Ra release kinetics were characterized by an initial burst release, which was reduced to a linear release over seven days. The mRNA expression levels and protein levels of IL-1β, MMP-1, MMP-3 and MMP-13 were reduced compared with the control group. The present study demonstrated the chondroprotective properties of CS microspheres as a controlled release system carrying IL-1Ra, due to the ability of the system to downregulate the expression of osteoarthritis-associated matrix-degrading proteinases in chondrocytes.

Context S -Propargyl-cysteine (SPRC), an endogenous H 2 S modulator, exerts anti-inflammatory effects on cardiovascular and neurodegenerative disease, but it remains unknown whether SPRC can prevent autoimmune hepatitis. Objective To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury and uncover the underlying mechanisms. Materials and methods Mice were randomly divided into five groups: control, Con A, SPRC (5 and 10 mg/kg injected intravenously once a day for 7 days), and propargylglycine (PAG; 50 mg/kg injected intraperitoneally 0.5 h before SPRC for 7 days). All mice except the controls were intravenously injected with Con A (20 mg/kg) on day 7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using kits. Inflammatory cytokines (TNF-α and IFN-γ) in the blood and in the liver were detected by ELISA Kit and real-time PCR, respectively. The expression of mitogen-activated protein kinase (MAPK) pathway proteins (p-JNK and p-Akt) and apoptosis proteins (Bax and Bcl-2) was detected using western blotting. Results SPRC reduced the levels of AST ( p < 0.05) and ALT ( p < 0.01) and decreased the release of the inflammatory cytokines. Mechanistically, SPRC increased H 2 S level ( p < 0.05) and promoted cystathionine γ-lyase (CSE) expression ( p < 0.05). SPRC inhibited the MAPK pathway activation and the apoptosis pathway. All the effects of SPRC were blocked by the CSE inhibitor PAG. Conclusions SPRC prevents Con A-induced liver injury in mice by promoting CSE expression and producing endogenous H 2 S. The mechanisms include reducing the release of inflammatory cytokines, attenuating MAPK pathway activation, and alleviating apoptosis.