Ankylosing spondylitis is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the spine and the sacroiliac joints. To date, the disease etiology remains unclear. In the present study, the correlation of T lymphocyte subset changes with the progression of ankylosing spondylitis was investigated. A total of 55 patients with ankylosing spondylitis (22 severe and 23 mild cases) and 20 healthy individuals were selected. Firstly, the punctured cells in the lesions and the serum were collected, and the lymphocytes and the peripheral blood mononuclear cells were prepared. Secondly, quantitative PCR, ELISA and flow cytometry analyses were carried out to detect the levels of a series of immunoglobulins, complements, helper T cells, cytotoxic T cells, regulatory cells and cytokines. The expression levels of α-globulin, γ-globulin, immunoglobulin (Ig)G, IgA, IgM, serum complement C3, and complement C4 were found to be significantly increased in ankylosing spondylitis patients. In addition, the percentage of Th1 and Th17 cells was found to be significantly higher in the ankylosing spondylitis groups (mild and severe) compared with the healthy individuals. As a result, the Th1/Th2 and Th17/Treg ratios were significantly higher in patients with ankylosing spondylitis. In addition, T lymphocyte subset ratio imbalances contributed to an increased expression of immune mediators, including interferon (IFN)-γ and interleukin (IL)-17A. The mRNA and protein expression levels of IFN-γ and IL-17A were found to be higher in the ankylosing spondylitis groups compared with the control group. The present study provided further evidence on the function and underlying mechanism of T lymphocyte subsets, which may be useful in the diagnosis and treatment of ankylosing spondylitis.

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Our study aimed to determine how lncRNA DANCR, miR-320a, and CTNNB1 interact with each other and regulate osteogenic differentiation in osteoporosis. qRT-PCR and western blotting were performed to determine the expression of DANCR, miR-320a, CTNNB1, and the osteoporosis- or Wnt/β-catenin pathway-related markers T-cell factor 1 (TCF-1), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Interactions between CTNNB1, DANCR, and miR-320a were predicted by bioinformatics approaches and validated using a luciferase assay. Osteoblastic phenotypes were evaluated by ALP staining, ALP activity assay and Alizarin Red staining. The bilateral ovariectomy method was used to establish an in vivo osteoporosis model. Bone morphological changes were examined using hematoxylin and eosin (H&E) and Alcian Blue staining. The expression levels of DANCR and miR-320a in BMSCs derived from osteoporosis patients were upregulated, whereas CTNNB1 expression was downregulated compared with that in healthy controls. Importantly, we demonstrated that miR-320a and DANCR acted independently from each other and both inhibited CTNNB1 expression, whereas the inhibitory effect was additive when miR-320a and DANCR were cooverexpressed. Moreover, we found that DANCR overexpression largely abrogated the effect of the miR-320a inhibitor on CTNNB1 expression and the Wnt/β-catenin signaling pathway in BMSCs during osteogenic differentiation. We further confirmed the results above in BMSCs derived from an osteoporosis animal model. Taken together, our findings revealed that DANCR and miR-320a regulated the Wnt/β-catenin signaling pathway during osteogenic differentiation in osteoporosis through CTNNB1 inhibition. Our results highlight the potential value of DANCR and miR-320a as promising therapeutic targets for osteoporosis treatment.

Background Diabetic foot ulcer (DFU) remains a serious chronic diabetic complication that can lead to disability. CircRNA‐itchy E3 ubiquitin protein ligase (circ‐ITCH) was observed to be down‐regulated in diabetic retinopathy and diabetic nephropathy, and overexpression of circ‐ITCH could inhibit the processes of these diseases. However, the detailed physiological and pathological functions of circ‐ITCH in wound healing of DFU remain undetermined. Methods Exosomes derived from bone marrow stromal cells (BMSCs) were isolated and identified. Cell viability and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit‐8 (CCK‐8) and tube formation assays, respectively. The interplays of circ‐ITCH, TATA‐Box‐binding protein associated factor 15 (TAF15) and nuclear factor erythroid 2‐related factor 2 (Nrf2) mRNA were analysed by RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) combined immunofluorescent staining and RNA pull‐down assays. qRT‐PCR, western blot or immunohistochemistry (IHC) were used to measure the expression of circ‐ITCH, TAF15, Nrf2, vascular endothelial growth factor (VEGFR) and ferroptosis‐related makers. The mice DFU model was established to verify the in vitro results. Results Circ‐ITCH was down‐regulated in in vitro and in vivo models of DFU. Deferoxamine (DFO), an iron chelating agent, improved the viability and angiogenic ability of high glucose (HG)‐treated HUVECs. Overexpression of circ‐ITCH or co‐cultured with exosomal circ‐ITCH from BMSCs could alleviate HG‐induced ferroptosis and improve the angiogenesis ability of HUVECs. Circ‐ITCH in HUVECs recruited TAF15 protein to stabilize Nrf2 mRNA, thus activating the Nrf2 signalling pathway and suppressing ferroptosis. Exosomal circ‐ITCH from BMSCs also accelerated the wound healing process by inhibiting ferroptosis in the DFU mice in a time‐dependent manner. Conclusion Exosomal circ‐ITCH from BMSCs inhibited ferroptosis and improved the angiogenesis of HUVECs through activation of the Nrf2 signalling pathway by recruiting TAF15 protein, ultimately accelerating the wound healing process in DFU.