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AimsMicroRNA-183 ( miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms.MethodsClinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 ( CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α ( TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 ( TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 ( Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 ( CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG.ResultsmiR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines ( IL-6, IL-1β, TNF-α) and pain-related factors ( TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα.ConclusionOur data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα- CCL2/ CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557.

Background. High tibial osteotomy (HTO) is an effective surgery in treating medial compartment knee osteoarthritis (KOA) combined with varus deformity. An accurate orthopaedy is the key and challenge to the success of HTO. Therefore, we designed a calibratable patient-specific instrumentation (PSI) to assist surgery and evaluated its accuracy and clinical outcomes by comparing with conventional operation (CO). Materials and Methods. 37 patients (39 knees) with medial compartment KOA were randomly divided into the PSI and CO groups and underwent medial open-wedge high tibial osteotomy (MOWHTO) from September 2020 to May 2021. The postoperative radiological outcomes were compared with the preoperative measurements or target values to evaluate the accuracy of correction in the two groups. The American Knee Society Score (AKSS), complication rate, number of intraoperative radiation exposures, blood loss volume, and operative duration were analysed to evaluate the clinical outcomes in the two groups. Results. The designed target values were better achieved in the PSI group than in the CO group. The mean absolute difference between the postoperative measurements and preoperative targets was significantly lower in the PSI group than in the CO group (weight-bearing line (WBL) ratio, 1.97 ± 1.83 % vs .5.42 ± 4.41 % , P = 0.002 ; hip-knee-ankle (HKA) angle, 1.12 ± 0.86 ° vs. 2.27 ± 1.97 °, P = 0.018 ). The operative duration was significantly shorter ( P = 0.014 ), and the number of radiation exposures ( P < 0.001 ) and volume of intraoperative blood loss ( P = 0.003 ) were significantly lower in the PSI group than in the CO group. The clinical AKSS score at 3 and 6 months postoperatively and the functional AKSS score at 3 months postoperatively were significantly higher in the PSI group than in the CO group ( P = 0.042 , 0.040, and 0.034, respectively). Conclusion. For patients with medial compartment KOA, calibratable PSI can assist the surgeon in MOWHTO with superior accuracy and clinical efficacy. This study was conducted under Randomized Controlled Trial Details (RCT) with Registry Number ChiCTR2000038619.

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. Dysregulated autophagy is a major cause of OA. However, the underlying mechanism is unclear. Here, we found that the expression of element-binding protein (CREB) was downregulated in both cartilage tissues of OA patients and mouse OA model. In tert-butyl hydroperoxide solution-treated chondrocytes, increased apoptosis and autophagic blockage were attenuated by CREB overexpression. Mechanically, MiR-373 directly targeted the 3'UTR of methyltransferase-like 3 (METTL3) and led to its downregulation. METTL3 epigenetically suppressed TFEB. The upregulation of miR-373 by CREB overexpression induced the release of TFEB from METTL3 and restored the autophagy activity of chondrocytes. Taken together, our study showed that CREB alleviates OA injury through regulating the expression of miR-373, which directly targeted METTL3, and finally relieved TFEB from METTL3-mediated epigenetic suppression. The CREB/miR-373/METTL3/TFEB axis may be used as a potential target for the treatment of OA.

Osteoarthritis (OA) represents a progressive degenerative disorder that predominantly affects the synovial membranes of joints. Recent studies have highlighted the significant role played by microRNAs (miRNAs) in OA development. The current study aimed to elucidate the underlying modulatory role of miR-27b-3p in the development of OA. The expression of miR-27b-3p in the OA patients and rat models post anterior cruciate ligament transection operation was measured using reverse transcription quantitative polymerase chain reaction, through which overexpressed miR-27b-3p was found in both of the samples. To further explore the miR-27b-3p functions in OA, western blot analysis, enzyme-linked immunosorbent assay, and β-galactosidase activity assay were conducted with the results showing that knockdown of miR-27b-3p promoted expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, inflammatory factors, and cellular senescence of bone marrow mesenchymal stem cells (BMSCs). After that, the interactions between miR-27b-3p, lysine Demethylase 4B (KDM4B), and Distal-Less Homeobox 5 (DLX5) identified using dual-luciferase reporter gene assay and ChIP assay revealed that miR-27b-3p inhibited KDM4B and further reduced expression of DLX5. Finally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed in rat models, and increased PWT and PWL were detected after miR-27b-3p silencing. In conclusion, suppression of miR-27b-3p could enhance KDM4B and DLX5 to alleviate OA pain, shedding light on a new potential therapeutic target for OA.

MicroRNA (miR)-133b has been reported to act as a tumor suppressor in multiple types of human cancers, including non small cell lung cancer (NSCLC). However, the underlying mechanism by which miR-133b inhibits NSCLC metastasis remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect messenger RNA and protein expression. A wound healing assay and transwell assay were used to examine the cell migration and invasion. The expression level of miR-133b was found to be significantly downregulated in NSCLC cell lines compared with normal lung epithelial BEAS-2B cells. Further investigation identified fascin1 (FSCN1) as a direct target of miR-133b in NSCLC cells. The expression of FSCN1 was significantly increased in NSCLC cell lines compared with BEAS-2B cells, and its protein expression was negatively regulated by miR-133b in NSCLC A549 cells. Further investigation showed that the upregulation of miR-133b notably inhibited NSCLC cell migration and invasion, while the overexpression of FSCN1 significantly promoted NSCLC cell migration and invasion. Furthermore, the overexpression of FSCN1 reversed the suppressive effect of miR-133b overexpression on NSCLC cell migration and invasion. Accordingly, the present study suggests that miR-133b inhibits the migration and invasion of NSCLC cells via directly targeting FSCN1, and thus may be used for the treatment of NSCLC metastasis.

To assess the effectiveness of two osteotomy methods in total hip arthroplasty (THA) for treating Crowe type IV adult developmental dysplasia of the hip (DDH), trochanteric osteotomy and subtrochanteric osteotomy.A retrospective analysis was made on the clinical data of 36 patients (43 hips) with Crowe type IV DDH undergoing THA between June 2007 and December 2013. In THA, 19 patients (23 hips) underwent trochanteric osteotomy (group A) and 17 patients (20 hips) underwent subtrochanteric osteotomy (group B). There was no significant difference in age, gender, body mass index, side, preoperative Harris score, and limb length difference between 2 groups (P0.05). The operation duration, bleeding volume, hospitalization duration, intraoperative and postoperative complications were compared between 2 groups.There was no significant difference in operation duration, bleeding volume, and hospitalization days between 2 groups (P0.05). The rate of intraoperative complication was 21.7% (5/23) in group A and 5.0% (1/20) in group B, showing no significant difference between 2 groups (P0.05). The rate of postoperative complications was 10.5% (2/19) in group A and 22.2% (4/18) in group B, showing no significant difference between 2 groups (P0.05). Thirty-one patients (37 hips) were followed up 1-7 years (mean, 3 years), including 16 cases (19 hips) in group A and 15 cases (18 hips) in group B. X-ray films showed good position of the prostheses. The Harris score at last follow-up was significantly increased when compared with preoperative score in 2 groups (P0.05), but there was no significant difference between 2 groups (P0.05). The postoperative discrepancy of bilateral lower limbs had no significant difference (t = -1.343, P=0.188).THA with trochanteric osteotomy or subtrochanteric osteotomy both can effectively treat Crowe type IV DDH. THA with subtrochanteric osteotomy has an advantage in correcting lower limb discrepancy.