Circ_0044235 regulates the development of osteoarthritis by the modulation of miR-375/PIK3R3 axis.

BACKGROUND: Circular RNAs (circRNAs) play an important role in osteoarthritis (OA). However, the role of circRNA in OA is still unclear. Here, we explored the role and mechanism of circ_0044235 in OA. METHODS: CHON-001 cells were treated with IL-1ß to establish OA model in vitro. The levels of circ_0044235, miR-375 and phosphoinositide 3-kinase (PI3K) regulatory subunit 3 (PIK3R3) were detected by quantitative real-time PCR. Cell count kit-8 assay and flow cytometry assay were used to detect cell viability and apoptosis. The concentrations of inflammation factors were determined by enzyme-linked immunosorbent assay. Western blot was used to detect protein levels. The interaction between miR-375 and circ_0044235 or PIK3R3 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: Circ_0044235 was significantly decreased in OA cartilage tissue and IL-1ß-treated CHON-001 cells. Overexpression of circ_0044235 promoted IL-1ß-stimulated CHON-001 cell viability and inhibited apoptosis, inflammation, and extracellular matrix (ECM) degradation. In mechanism analysis, circ_0044235 could act as a sponge for miR-375 and positively regulate PIK3R3 expression. In addition, miR-375 ameliorated the effect of circ_0044235 overexpression on IL-1ß-mediated CHON-001 cells injury. In addition, miR-375 inhibition mitigated IL-1ß-induced CHON-001 cell injury, while PIK3R3 silencing restored the effect. CONCLUSION: Circ_0044235 knockdown alleviated IL-1ß-induced chondrocytes injury by regulating miR-375/PIK3R3 axis, confirming that circ_0044235 might be a potential target for OA treatment.

Biomechanics of PHILOS plates in Vancouver B1 periprosthetic femoral fracture.

Objective: To investigate the clinical efficacy of PHILOS plates in the treatment of Vancouver B1 periprosthetic femoral fracture (PFF) and to validate its biomechanical reliability via finite element analysis and mechanical testing on the Synbone femoral models. Methods: Ten males and eight females with Vancouver B1 PFF who underwent PHILOS plate fixation between September 2017 and January 2022 were selected. The average age was 72.61 ± 8.19 years, with a range of 57-86 years old. X-ray films were taken to assess the fracture healing situation around the femoral prosthesis as well as the position of the PHILOS plates and femoral prosthesis. Two different plates (the PHILOS plate and the Cable GTR plate) were used for fixation, and the differences in biomechanical stability of the two fixation methods were compared using finite element analysis and mechanical testing on the Synbone femoral models to validate the biomechanical dependability of the PHILOS plate. Results: All 18 cases were followed for at least 1 year, as a result. The average period of follow-up was 17 months, ranging from 12 to 36 months. At the most recent follow-up, Harris scores for the hip joints of patients ranged from 82 to 89, with an average score of 86. The X-rays revealed that all fractures surrounding the femoral prosthesis had healed and that there was no looseness in the femoral prosthesis. None of the PHILOS license plates had expired. All patients were able to perform full-load walking, and pain and claudication in affected limbs were significantly reduced. Finite element analysis and mechanical testing of the Synbone femoral model revealed that the fixation effect of the PHILOS group was superior to that of the Cable group; consequently, PHILOS plates can be used to effectively fix fractures around the proximal femoral prosthesis. Conclusion: PHILOS plates are initially used in the treatment of Vancouver B1 PFF, which may be a good choice due to their simpler operation, lower medical costs, and satisfactory clinical efficacy.

Pilose antler peptide promotes osteoblast proliferation, differentiation and mineralization via the insulin signaling pathway.

Osteoporosis is a severe bone disease characterized by a decrease in the density and structure of bones, with high risks of fractures. Pilose antler peptide (PAP), extracted and purified from deer antlers, can promote regeneration and fracture healing, and strengthen sinews and bone. To determine whether PAP can promote osteoblast development and to elucidate the molecular mechanisms underlying its functions, the present study investigated the effects of PAP on osteoblast proliferation, differentiation and mineralization, and the role of the insulin signaling pathway using MTT assay, alkaline phosphatase activity assay, western blot analysis and reverse transcription-quantitative PCR. The present results suggested that PAP promoted osteoblast proliferation, differentiation and mineralization in vitro via the insulin signaling pathway. The effect of PAP on insulin signaling in osteoblasts may be mediated via the ERK pathway and partially by the PI3K/Akt pathway. The present results indicated that PAP could potentially be developed as an alternative treatment strategy for bone diseases related to diabetes characterized by insulin signaling impairment.

Isoliquiritigenin inhibits melanogenesis, melanocyte dendricity and melanosome transport by regulating ERK-mediated MITF degradation.

Isoliquiritigenin (ISL), a flavonoid component from the hydrolysis products of licorice root. It has been reported that ISL inhibited melanogenesis by suppressing the tyrosinase activity in human melanocytes. Recently, ISL was found to induce melanin degradation in human epidermal keratinocytes. However, the role of ISL in pigmentation is not fully understood. In the current study, we aimed to investigate the effects of ISL on pigmentation, and further explored the underlying mechanism. Our results suggested that ISL suppressed basal and α-MSH-, ACTH- and UV-induced melanin synthesis, in addition to inhibiting melanocyte dendricity and melanosome transport. ISL played these roles mainly by activating the extracellular signal-regulated protein kinase pathway. Once activated, it induced microphthalmia-associated transcription factor degradation and decreased the expression of tyrosinase, TRP-1, DCT, Rab27a and Cdc42, finally inhibited melanogenesis, melanocyte dendricity and melanosome transport. Our findings suggested that ISL exhibited no cytotoxicity in our research, it may prove quite useful as a safer natural skin-whitening agent.

Diazepam enhances melanogenesis, melanocyte dendricity and melanosome transport via the PBR/cAMP/PKA pathway.

Diazepam is a medicament of the benzodiazepine family and it typically produces a sedative effect. Researchers have revealed that diazepam can induce melanogenesis and produce dendrite-like structures in B16 melanoma cells. However, the associated mechanisms of melanogenesis and phenotypic alterations have mostly remained unknown. In this study, we determined the effects of diazepam on melanogenesis, cellular phenotypic alterations, the location of melanosomes and the expression of relevant proteins in melanocytes using Masson-Fontana ammoniacal silver staining, scanning electron microscopy, immunocytochemistry and western blot analysis. Our results collectively indicated that diazepam had a pivotal role in melanocytes by enhancing melanin synthesis, melanocyte dendricity, melanosome trafficking, and capture at the dendrite tips. These functions might be attributed to the fact that diazepam activated the peripheral benzodiazepine receptor (PBR). This increased intracellular levels of cAMP, which stimulated the phosphorylation of cAMP response element-binding (CREB). As a result, this increased the tyrosinase, microphthalmia-associated transcription factor (MITF), Rab27a, Myosin Va, Rab17 and Cdc42 expression. This caused melanogenesis and melanosome transport. Therefore, our findings may provide a potential strategy for treating anti-hypopigmentation disorders.

Clinical and radiographic outcomes of treatment of comminuted Mason type II radial head fractures with a new implant.

This study aims to evaluate the clinical and radiographic treatment outcomes of comminuted Mason type II radial head fractures, which underwent open reduction and internal fixation (ORIF) using a new implant (mother-child screw, MCS).This study included 16 patients (7 male and 9 female patients; mean age: 40.9 years, age range: 19-68 years), who were treated with ORIF, followed by MCS fixation for comminuted type II radial head fractures. The clinical results were evaluated using the Mayo Elbow Performance Score (MEPS). Radiographs, which included the quality of fracture reduction, stability, osteoarthritis, and heterotopic ossification of the elbow, were investigated. The mean follow-up period was 23.4 months.Anatomical reduction and bone union were achieved in all patients treated with MCS, and mean union time was 6.2 weeks. The average flexion-extension arc of elbow motion was 135.6° (range: 125°-150°), and the average arc of forearm rotation was 155.3° (range: 145°-170°). Furthermore, MEPS was 94.1 (range: 85-100), and the rate of excellent and good was 100%. All patients returned to preinjury work within a mean period of 11.7 weeks. No heterotopic ossification and joint stiffness of the elbow were encountered. Two patients had mild arthritic changes (grade I), but none of these patients complained of pain.The use of MCS fixation for comminuted type II radial head fractures resulted in good clinical and radiographic outcomes.