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Osteoarthritis (OA) is the second-commonest arthritis, but pathogenic and regulatory mechanisms underlying OA remain incompletely understood. Here, we aimed to identify the mechanisms associated with microRNA-1 (miR-1) treatment of OA in rodent OA models using a proteomic approach. First, N = 18 Sprague Dawley (SD) rats underwent sham surgery (n = 6) or ACL transection (n = 12), followed at an interval of one week by randomization of the ACL transection group to intra-articular administration of either 50 µL placebo (control group) or miR-1 agomir, a mimic of endogenous miR-1 (experimental group). After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and immunohistochemically stained for the presence of MMP-13. Second, N = 30 Col2a1-cre-ERT2 /GFPf1/fl -RFP-miR-1 transgenic mice were randomized to intra-articular administration of either placebo (control group, N = 15) or tamoxifen, an inducer of miR-1 expression (experimental group, N = 15), before undergoing surgical disruption of the medial meniscus (DMM) after an interval of five days. After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and underwent differential proteomic analysis. Specifically, tandem mass tagging (TMT) quantitative proteomic analysis was employed to identify inter-group differentially-expressed proteins (DEP), and selected DEPs were validated using real-time quantitative polymerase chain reaction (RT-qPCR) technology. Immunohistochemically-detected MMP-13 expression was significantly lower in the experimental rat group, and proteomic analyses of mouse tissue homogenate demonstrated that of 3526 identified proteins, 345 were differentially expressed (relative up- and down-regulation) in the experimental group. Proteins Fn1, P4ha1, P4ha2, Acan, F2, Col3a1, Fga, Rps29, Rpl34, and Fgg were the *top ten most-connected proteins, implying that miR-1 may regulate an expression network involving these proteins. Of these ten proteins, three were selected for further validation by RT-qPCR: the transcript of Fn1, known to be associated with OA, exhibited relative upregulation in the experimental group, whereas the transcripts of P4ha1 and Acan exhibited relative downregulation. These proteins may thus represent key miR-1 targets during OA-regulatory mechanisms, and may provide additional insights regarding therapeutic mechanisms of miR-1 in context of OA. [ABSTRACT FROM AUTHOR]

Endochondral bone formation from the growth plate plays a critical role in vertebrate limb development and skeletal homeostasis. Although miR-1 is mainly expressed in the hypertrophic region of the growth plate during this process, its role in the endochondral bone formation is unknown. To elucidate the role of miR-1 in cartilage development, chondrocyte-specific transgenic mice with high expression of miR-1 were generated (Col2a1-Cre-ERT2-GFPfl/fl-RFP-miR-1). Transgenic mice showed short limbs and delayed formation of secondary ossification centers. In the tibia growth plate of miR-1-overexpressing transgenic mice, the chondrocytes in the proliferative zone were disorganized and their proliferation decreased, and the ColX, MMP-13 and Indian Hedgehog (IHH) in chondrocytes showed a downward trend, resulting in decreased terminal differentiation in the hypertrophic zone. In addition, the apoptosis index caspase-3 also showed a downward trend in the tibia growth plate. It was concluded that miR-1 overexpression affects chondrocyte proliferation, hypertrophic differentiation, and apoptosis, thereby delaying the formation of secondary ossification centers and leading to short limbs. It was also verified that miR-1 affects endochondral ossification through the IHH pathway. The above results suggest that miR-1 overexpression can affect endochondral osteogenesis by inhibiting chondrocyte proliferation, hypertrophic differentiation, and apoptosis, thus causing limb hypoplasia in mice. This work gives potential for new therapeutic directions and insights for the treatment of dwarf-related diseases. • We used the new Col2a1-Cre-ERT2-GFPfl/fl-RFP-miR-1 transgenic mouse model • MiR-1 overexpression caused delayed formation of secondary ossification centers and shortened extremities in mice • MiR-1 overexpression inhibits chondrocyte proliferation, hypertrophy, and apoptosis • MiR-1 may act through the Hh pathway [ABSTRACT FROM AUTHOR]

The development of heterogeneous Fenton catalysts with good performance and stability is a challenge in the field of wastewater treatment. In this work, MgAlFe hydrotalcite-like compounds (MgAlFe-HTLcs) were prepared by solid phase reaction at room temperature and modified via a hydrothermal process. The experimental results showed that MgAlFe-HTLcs had a good layered structure with the same proportion of iron and aluminium, 18 h of crystallisation time and 110°C of crystallisation temperature and the lamellar structure was more uniform by solid grinding. Furthermore, the addition of iron can activate H2O2 more effectively to generate active oxygen which is •OH. The degradation experiments demonstrated that nearly 99.0% degradation efficiency was achieved for 10 mg/L Malachite Green (MG) solution within 60 min at the conditions of 0.10 g·L−1 MgAlFe-HTLcs, 0.10 mol·L-1 H2O2 and a natural pH of 6.3. Total organic carbon (TOC) removal reached 72.2% in a 70 min reaction. BET and XRD were measured to further discuss the stability and durability. Finally, a possible mechanism for the degradation of MG was presumed. [ABSTRACT FROM AUTHOR]

Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague–Dawley rats aged 2–3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1β for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague–Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1β-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh. [ABSTRACT FROM AUTHOR]