Acceleration of healing of the medial collateral ligament of the knee by local administration of synthetic microRNA-210 in a rat model

AbstractBackgroundInjury to the medial collateral ligament (MCL) of the knee joint is the most common ligament injury of the knee. Ligament healing generally takes a long time. Micro-ribonucleic acid (miRNA) is one of the noncoding RNAs and plays a crucial role in physiological function; miRNA (miR)-210 is known as a potent factor of angiogenesis, which is an important initiator of ligament healing. The purpose of this study is to examine the effect of local injection of double-stranded (ds) miR-210 on the healing of the MCL of rat knee joint.MethodsMCLs of Sprague-Dawley rats were cut transversely. After the fascia and skin were sutured, dsmiR-210 or control dsRNA was injected into the injured site of MCL. At 2 weeks and 4 weeks, histological analysis and immunofluorescence staining of vascular endothelial growth factor, isolectin B4, collagen type 1, and Ki67 as well as a mechanical test were performed. Analysis of complementary deoxyribonucleic acid (cDNA) microarray data was performed at 1 week.ResultsHistological analysis showed that parallel fibres in the injured site were organised at 2 weeks and became thicker at 4 weeks in the miR-210-treated group, whereas the injured site in controls was filled with loose fibrous tissues and was thinner than that in the miR-210-treated group. The number of blood vessels in the miR-210-treated group was significantly higher than that in controls (p < 0.05), and vascular endothelial growth factor, Ki67, and collagen type 1 in the miR-210-treated group were intensely expressed in the repaired site as compared to the control group. The mechanical test indicated that the ultimate failure load in the miR-210-treated group was significantly higher than that in the control group at 2 weeks. The cDNA microarray analysis showed significant upregulation of genes related to cell proliferation and cell differentiation, and genes involved in negative regulation of apoptosis.ConclusionThis study showed that local injection of dsmiR-210 could accelerate MCL healing in rat, which is likely due to stimulation of angiogenesis at the healing site

Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis

Abstract Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor antagonist (rimegepant) could suppress OA progression and relieve pain in two OA models. C57BL/6 mice (10-week-old) underwent surgical destabilization of the medial meniscus, and Rimegepant (1.0 mg/kg/100 μL) or phosphate-buffered saline (100 μL) was administered weekly intraperitoneally after OA surgery and evaluated at 4, 8, and 12 weeks. In the senescence-accelerated mice (SAM)-prone 8 (SAMP8), rimegepant was administered weekly before and after subchondral bone sclerosis and sacrificed at 9 and 23 weeks, respectively. Behavioral assessment and immunohistochemical staining (CGRP) of the dorsal root ganglion (DRG) were conducted to assess pain. In DMM mice, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed in the rimegepant group. In SAMP8, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed by rimegepant at 9 weeks; however, not at 23 weeks. Behavioral assessment shows the traveled distance and the number of standings in the rimegepant group were significantly longer and higher. In addition, CGRP expression of the DRG was significantly lower in the rimegepant group at 8 and 12 weeks of DMM and 9 weeks of SAMP8 treatment. No adverse effects were observed in either of the mouse models. Inhibition of CGRP signaling has the potential to be a therapeutic target to prevent OA progression and suppress pain through the attenuation of subchondral bone sclerosis and synovitis