摘要: Objectives The aim of the study was to investigate the effect of matrix stiffness on arteriovenous differentiation of endothelial progenitor cells (EPCs) during vasculogenesis in nude mice. Materials and methods Dextran hydrogels of differing stiffnesses were first prepared by controlling the crosslinking reaction to generate different thioether bonds. Hydrogels with stiffnesses matching those of the arterial extracellular matrix and venous extracellular matrix were separately combined with mouse bone marrow-derived EPCs and subcutaneously implanted on either side of the backs of nude mice. After 14 days, artery-specific marker Efnb2 and vein-specific marker Ephb4 in the neovasculature were detected to determine the effect of matrix stiffness on the arteriovenous differentiation of EPCs in vivo. Results Fourteen days after the implantation of the EPC-loaded dextran hydrogels, new blood vessels were observed in both types of hydrogels. We further verified that matrix stiffness regulated the arteriovenous differentiation of EPCs during vasculogenesis via the Ras/Mek pathway. Conclusions Matrix stiffness regulates the arteriovenous differentiation of EPCs during vasculogenesis in nude mice through the Ras/Mek pathway.

摘要: Objectives Interleukin (IL)-37 is a natural suppressor of innate inflammation. This study was conducted to explore the anti-inflammatory effects of IL-37 in temporomandibular joint (TMJ) inflammation. Materials and Methods The expression of IL-37 in the TMJ was measured using ELISA and IHC. Human TMJ chondrocytes were treated with IL-37b and IL-1 beta, and inflammation-related factors were detected. siRNA-IL-1R8 was transfected into chondrocytes, and the affected pathways were detected. IL-37b was used in disc-perforation-induced TMJ inflammation in SD rats. Micro-CT, IHC, real-time PCR and histological staining were used to quantify the therapeutic effect of IL-37b. Results IL-37 was expressed in the synovium and the disc of patients with osteoarthritis (OA) and in the articular cartilage of condylar fracture patients. IL-37 was highly expressed in synovial fluid of patients with synovitis than in those with OA and disc displacement and was closely related to visual analogue scale (VAS) score. In vitro, IL-37b suppressed the expression of pro-inflammatory factors. In addition, IL-37b exerted anti-inflammatory effects via IL-1R8 by inhibiting the p38, ERK, JNK and NF-kappa B activation, while silencing IL-1R8 led to inflammation and upregulation of these signals. In disc-perforation-induced TMJ inflammation in SD rats, IL-37b suppressed inflammation and inhibited osteoclast formation to protect against TMJ. Conclusions IL-37b may be a novel therapeutic agent for TMJ inflammation.

摘要: Objectives Osteopetrosis is a rare inherited skeletal disease characterized by increased bone mineral density due to the loss of osteoclast function or differentiation potential. Materials and Methods The study involved a Chinese patient with osteopetrosis (the proband) and her immediate family members and 180 controls without osteopetrosis. Bone density of the femoral neck, lumbar spine and total body was measured using dual-energy x-ray absorptiometry. Osteoclast differentiation by the participants' peripheral blood mononuclear cells (PBMCs) was investigated using tartrate-resistant acid phosphatase (TRAP) staining. Osteoblast differentiation was examined with Alizarin Red S staining. Reverse transcription-quantitative PCR was used to amplify immunoglobulin superfamily member 23 (IGSF23), c-FOS and nuclear factor of activated T cells 1 (NFATC1). Results We found a homozygous mutation (c.295C>T) in the IGSF23 gene in two osteopetrosis samples. The mutation led to the formation of a stop codon, causing loss of the immunoglobulin-like domain and the whole transmembrane domain. PBMCs from the proband (IGSF23(-/-)) exhibited poor ability for differentiating into mature osteoclasts in vitro. Overexpression of IGSF23 rescued the ability of IGSF23(-/-) PBMCs to differentiate into osteoclasts. Moreover, knockdown of IGSF23 reversed the bone loss in OVX mice by injecting AAV-shIGSF23 into mice femoral bone marrow cavity. Furthermore, we also found that the IGSF23 mutation led to decreased c-Fos and NFATC1 expression levels by inhibiting the mitogen-activated protein kinase signalling pathways. Conclusions IGSF23-mediated osteoclast differentiation of PBMCs may serve as a potential target in osteoporosis therapy.

摘要: Objectives Emerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database. This study focused on the biological function and mechanism of lncRNA ABHD11-AS1 in PTC. Materials and methods qRT-PCR analysis was used to examine the expression of ABHD11-AS1 in PTC tissues and cell lines. The prognostic significance of ABHD11-AS1 for the patients with PTC was analysed with Kaplan-Meier analysis. The effects of ABHD11-AS1 knockdown on the cell proliferation and metastasis were evaluated by in vitro functional assays and in vivo experiments. The molecular mechanism which contributed to the oncogenic role of ABHD11-AS1 in PTC was explored by conducting mechanism experiments. Rescue assays were carried out for final demonstration. Results High expression of ABHD11-AS1 predicted poor prognosis for patients with PTC and promoted cell proliferation and metastasis in vitro and in vivo. ABHD11-AS1 was activated by the transcription factor STAT3. ABHD11-AS1 positively regulated PI3K/AKT signalling pathway. ABHD11-AS1 acted as a competitive endogenous (ce) RNA to upregulate STAT3 by sponging miR-1301-3p. Conclusions STAT3-induced lncRNA ABHD11-AS1 promoted PTC progression by regulating PI3K/AKT signalling pathway and miR-1301-3p/STAT3 axis.

摘要: Objective It is essential to characterize underlying molecular mechanism associated with head and neck squamous cell carcinoma (HNSCC) and identify promising therapeutic targets. Herein, we explored role of homeobox transcript antisense RNA (HOTAIR) in HNSCC to regulate stanniocalcin-2 (STC2) by sponging microRNA-206 (miR-206). Methods HNSCC-related differentially expressed genes and regulation network amongst HOTAIR, miR-206 and STC2 were identified. Next, effect of HOTAIR on cell biological functions of HNSCC was identified after transfection of cells with HOTAIR overexpressed plasmids or siRNA against HOTAIR. PI3K/AKT signalling pathway-related gene expression was measured after miR-206 and STC2 were suppressed. Cell invasion, migration and proliferation were assessed. Finally, tumour growth was assessed to determine the effects of HOTAIR/miR-206/STC2 axis in vivo. Results HOTAIR specifically bound to miR-206 and miR-206 targeted STC2. Downregulated HOTAIR or upregulated miR-206 suppressed HNSCC cell proliferation, invasion and migration. miR-206 inhibited PI3K/AKT signalling pathway by down-regulating STC2. Besides, silenced HOTAIR or overexpressed miR-206 repressed the tumour growth of nude mice with HNSCC. Conclusion HOTAIR regulated HNSCC cell biological functions by binding to miR-206 through STC2.