Delivery of miR-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting GFAP.

Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.

Extracellular vesicles derived from bone marrow mesenchymal stem cells loaded on magnetic nanoparticles delay the progression of diabetic osteoporosis via delivery of miR-150-5p.

Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) are emerged as carriers of therapeutic targets against bone disorders, yet its isolation and purification are limited with recent techniques. Magnetic nanoparticles (MNPs) can load EVs with a unique targeted drug delivery system. We constructed gold-coated magnetic nanoparticles (GMNPs) by decorating the surface of the Fe3O4@SiO2 core and a silica shell with poly(ethylene glycol) (PEG)-aldehyde (CHO) and examined the role of BMSC-EVs loaded on GMNPs in diabetic osteoporosis (DO). The osteoporosis-related differentially expressed miR-150-5p was singled out by microarray analysis. DO models were then established in Sprague-Dawley rats by streptozotocin injection, where poor expression of miR-150-5p was validated in the bone tissues. Next, GMNPE was prepared by combining GMNPs with anti-CD63, after which osteoblasts were co-cultured with the GMNPE-BMSC-EVs. The re-expression of miR-150-5p facilitated osteogenesis in osteoblasts. GMNPE could promote the enrichment of EVs in the bone tissues of DO rats. BMSC-EVs delivered miR-150-5p to osteoblasts, where miR-150-5p targeted MMP14 and consequently activated Wnt/ß-catenin pathway. This effect contributed to the enhancement of osteoblast proliferation and maturation. Furthermore, GMNPE enhanced the EV-based delivery of miR-150-5p to regulate the MMP14/Wnt/ß-catenin axis, resulting in promotion of osteogenesis. Overall, our findings suggest the potential of GMNP-BMSC-EVs to strengthen osteoblast proliferation and maturation in DO, showing promise as an appealing drug delivery strategy against DO. 1. GMNPs-BMSCs-EVs-miR-150-5p promotes the osteogenesis of DO rats. 2. miR-150-5p induces osteoblast proliferation and maturation by targeting MMP14. 3. Inhibition of MMP14 activates Wnt/ß-catenin and increases osteogenesis. 4. miR-150-5p activates the Wnt/ß-catenin pathway by downregulating MMP14.

Harnessing GMNP-loaded BMSC-derived EVs to target miR-3064-5p via MEG3 overexpression: Implications for diabetic osteoporosis therapy in rats.

Diabetic osteoporosis (DO) is a significant complication of diabetes, characterized by a decrease in bone mineral density and an increase in fracture risk. Magnetic nanoparticles (GMNPs) have emerged as potential drug carriers for various therapeutic applications. This study investigated the molecular mechanism of GMNPs loaded with bone marrow mesenchymal stem cell (BMSC) derived extracellular vesicles (EVs) overexpressing MEG3 target miR-3064-5p to induce NR4A3 for treating DO in rats. Initial analysis was carried out on GEO datasets GSE7158 and GSE62589, revealing a notable downregulation of NR4A3 in osteoporotic samples. Subsequent in vitro studies demonstrated the effective uptake of BMSC-EVs-MEG3 by osteoblasts and its potential to inhibit miR-3064-5p, activating the PINK1/Parkin signaling pathway and thus promoting mitochondrial autophagy, osteoblast proliferation, and differentiation. In vivo, experiments using DO rat models further substantiated the therapeutic efficacy of GMNPE-EVs-MEG3 in alleviating osteoporosis symptoms. In conclusion, GMNPs loaded with BMSC-EVs, through the delivery of MEG3 targeting miR-3064-5p, can effectively promote NR4A3 expression, activate the PINK1/Parkin pathway, and thereby enhance osteoblast proliferation and differentiation, offering a promising treatment for DO.

[Short-term effectiveness of robot-guided femoral neck system combined with cannulated compression screw fixation in treatment of femoral neck fracture in young and middle-aged patients].

Objective: To investigate short-term effectiveness of robot-guided femoral neck system (FNS) combined with cannulated compression screw (CCS) fixation in treatment of femoral neck fracture in young and middle-aged patients. Methods: A clinical data of 49 young and middle-aged patients with femoral neck fractures, who met the selection criteria and admitted between January 2021 and June 2023, was retrospectively analyzed. After reduction of femoral neck fractures, 27 cases were treated with robot-guided FNS fixation (FNS group) and 22 cases with robot-guided FNS and CCS fixation (FNS+CCS group). There was no significant difference in baseline data such as gender, age, cause of fracture, time from fracture to operation, fracture side, and classification (Garden classification and Pauwels classification) between the two groups ( P>0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, the time when the patient began bearing weight, and hip joint pain and functional scores (VAS score and Harris score) at last follow-up for two groups were recorded. Imaging re-examination was taken to evaluate the quality of fracture reduction, fracture healing, as well as the occurrence of fracture non-union, osteonecrosis of the femoral head, and femoral neck shortening. Results: All operations were successfully completed and the incisions healed by first intention. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05), and the intraoperative fluoroscopy frequency in FNS+CCS group significantly increased compared to FNS group ( P<0.05). All patients were followed up 12-18 months (mean, 14.1 months). Imaging re-examination showed that there was no significant difference in fracture reduction quality between the two groups ( P>0.05), but the fracture healing time was significantly shorter in FNS+CCS group than in FNS group, and weight-bearing began earlier ( P<0.05). The incidences of femoral neck shortening, fracture non-union, and osteonecrosis of the femoral head were lower in FNS+CCS group than in FNS group, and there was significant difference in the incidence of femoral neck shortening between groups ( P<0.05). At last follow-up, there was no significant difference in VAS scores between the two groups ( P>0.05). However, the Harris score was significantly higher in FNS+CCS group than in FNS group ( P<0.05). Conclusion: Compared with FNS fixation alone, robot-guided FNS combined with CCS fixation in the treatment of femoral neck fractures in young and middle-aged patients has obvious advantages in terms of early weight bearing and fracture healing, improves fracture healing rate, effectively prevents postoperative complications, and can obtain good short-term effectiveness.

[Early effectiveness of Ti-Robot assisted femoral neck system for minimally invasive treatment of elderly Garden type â ¡ and â ¢ femoral neck fractures].

Objective: To investigate the early effectiveness of the Ti-Robot assisted femoral neck system (FNS) in the treatment of elderly Garden type Ⅱ and Ⅲ femoral neck fractures. Methods: A retrospective analysis was conducted on the clinical data of 41 elderly patients with Garden type Ⅱ and Ⅲ femoral neck fractures who were admitted between December 2019 and August 2022 and met the selection criteria. Among them, 21 cases were treated with Ti-Robot assisted FNS internal fixation (study group), and 20 cases were treated solely with FNS internal fixation (control group). There was no significant difference in baseline data, including gender, age, side, cause of injury, time from injury to surgery, fracture Garden classification, and fracture line classification, between the two groups ( P>0.05). Surgical effectiveness was evaluated based on parameters such as operation time (including incision time and total operation time), reduction level, number of dominant pin insertions, intraoperative fluoroscopy frequency, incision length, whether to extend the incision, need for assisted reduction, postoperative hospital stay, fracture healing time, incidence of osteonecrosis of the femoral head, postoperative visual analogue scale (VAS) score at 1 day, and Harris hip score at last follow-up. Results: The study group showed significantly shorter incision time, fewer dominant pin insertions, fewer instances of extended incisions, fewer intraoperative fluoroscopy frequency, and smaller incisions than the control group ( P<0.05). There was no significant difference in total operation time, reduction level, and assisted reduction frequency between the two groups ( P>0.05). Both groups achieved primary wound healing postoperatively, with no complications such as incision leakage or skin infection. All patients were followed up 12-24 months with an average of 14.6 months. Fractures healed in both groups, with no significant difference in healing time ( P>0.05). There was no significant difference in postoperative hospital stay between the two groups ( P>0.05). The study group showed significantly better VAS score at 1 day after operation and Harris hip score at last follow-up when compared to the control group ( P<0.05). No complication such as internal fixation failure, fracture displacement, or hip joint varus occurred in both groups during the follow-up. Osteonecrosis of the femoral head occurred in 1 patient of the control group, while no was observed in the study group, and the difference in the incidence of osteonecrosis of the femoral head between the two groups was not significant ( P=0.488). Conclusion: Compared to sole FNS internal fixation treatment, Ti-Robot assisted FNS internal fixation for elderly Garden typeⅡ and Ⅲ femoral neck fractures can reduce incision time, achieve minimally invasive and accurate nail implantation, and decrease intraoperative fluoroscopy frequency, leading to improved postoperative hip joint function recovery.

[Study on application of ultrasonic bone curette in anterior cervical spine surgery].

Objective: To investigate the effect of ultrasonic bone curette in anterior cervical spine surgery. Methods: A clinical data of 63 patients with cervical spondylosis who were admitted between September 2019 and June 2021 and met the selection criteria was retrospectively analyzed. Among them, 32 cases were operated with conventional instruments (group A) and 31 cases with ultrasonic bone curette (group B). There was no significant difference between the two groups (P>0.05) in gender, age, surgical procedure, surgical segment and number of occupied cervical space, disease type and duration, comorbidities, and preoperative Japanese Orthopaedic Association (JOA) score, cervical dysfunction index (NDI), and pain visual analogue scale (VAS) score. The operation time, intraoperative bleeding, postoperative drainage, postoperative hospital stay, and the occurrence of postoperative complications were recorded in both groups. Before operation and at 1, 3, and 6 months after operation, the JOA score and NDI were used to evaluate the function and the postoperative JOA improvement rate was calculated, and VAS score was used to evaluate the pain improvement. The anteroposterior and lateral cervical X-ray films were taken at 1, 3, and 6 months after operation to observe whether there was any significant loosening and displacement of internal fixators. Results: Compared with group A, group B had shorter operation time and postoperative hospital stay, less intraoperative bleeding and postoperative drainage, and the differences were significant (P<0.05). All incisions healed by first intention in the two groups, and postoperative complications occurred in 5 cases (15.6%) in group A and 2 cases (6.5%) in group B, showing no significant difference (P>0.05). All patients were followed up 6-12 months (mean, 7.9 months). The JOA score and improvement rate gradually increased in groups A and B after operation, while the VAS score and NDI gradually decreased. There was no significant difference in VAS score between 3 months and 1 month in group B (P>0.05), and there were significant differences between the other time points of each indicator in the two groups (P<0.05). At 1, 3, and 6 months after operation, the JOA score and improvement rate in group B were better than those in group A (P<0.05). X-ray films examination showed that there was no screw loosening or titanium plate displacement in the two groups after operation, and the intervertebral cage or titanium mesh significantly sank. Conclusion: Compared with traditional instruments, the use of ultrasonic bone curette assisted osteotomy in anterior cervical spine surgery has the advantages of shorter operation time, less intraoperative bleeding, less postoperative drainage, and shorter hospital stay.

[Research progress of exosomes in treatment of osteoporosis].

OBJECTIVE: To review the research progress of exosomes (EXOs) derived from different cells in the treatment of osteoporosis (OP). METHODS: Recent relevant literature about EXOs for OP therapy was extensively reviewed. And the related mechanism and clinical application prospect of EXOs derived from different cells in OP therapy were summarized and analyzed. RESULTS: EXOs derived from various cells, including bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, osteocytes, and endothelial cells, et al, can participate in many links in the process of bone remodeling, and their mechanisms involve the regulation of proliferation and differentiation of bone-related cells, the promotion of vascular regeneration and immune regulation, and the suppression of inflammatory reactions. A variety of bioactive substances contained in EXOs are the basis of regulating the process of bone remodeling, and the combination of genetic engineering technology and EXOs-based drug delivery can further improve the therapeutic effect of OP. CONCLUSION: EXOs derived from different cells have great therapeutic effects on OP, and have the advantages of low immunogenicity, high stability, strong targeting ability, and easy storage. EXOs has broad clinical application prospects and is expected to become a new strategy for OP treatment.