Osteoporosis is a common systemic bone disease caused by the imbalance between osteogenic activity and osteoclastic activity. Aged women are at higher risk of osteoporosis, partly because of estrogen deficiency. However, the underlying mechanism of how estrogen deficiency affects osteoclast activity has not yet been well elucidated. In this study, GSE2208 and GSE56815 datasets were downloaded from GEO database with 25 PreH BMD women and 25 PostL BMD women in total. The RRA algorithm determined 38 downregulated DEGs and 30 upregulated DEGs. Through GO analysis, we found that downregulated DEGs were mainly enriched in myeloid cell differentiation, cytokine-related functions while upregulated DEGs enriched in immune-related biological processes; pathways like Notch signaling and MAPK activation were found in KEGG/Rectome pathway database; a PPI network which contains 66 nodes and 91 edges was constructed and three Modules were obtained by Mcode; Correlation analysis helped us to find highly correlated genes in each module. Moreover, three hub genes FOS, PTPN6, and CTSD were captured by Cytohubba. Finally, the hub genes were further confirmed in blood monocytes of ovariectomy (OVX) rats by real-time PCR assay. In conclusion, the integrative bioinformatics analysis and real-time PCR analysis were utilized to offer fresh light into the role of monocytes in premenopausal osteoporosis and identified FOS, PTPN6, and CTSD as potential biomarkers for postmenopausal osteoporosis.

Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple lineages, making MSC transplantation a promising option for bone regeneration. Both matricellular proteins and growth factors play an important role in regulating stem cell fate. In this study, we investigated the effects of matricellular protein SMOC2 (secreted modular calcium-binding protein 2) on bone morphogenetic protein 9 (BMP9) in mouse embryonic fibroblasts (MEFs) and revealed a possible molecular mechanism underlying this process. We found that SMOC2 was detectable in MEFs and that exogenous SMOC2 expression potentiated BMP9-induced osteogenic markers, matrix mineralization, and ectopic bone formation, whereas SMOC2 knockdown inhibited these effects. BMP9 increased the levels of p-FAK and p-AKT, which were either enhanced or reduced by SMOC2 and FAK silencing, respectively. BMP9-induced osteogenic markers were increased by SMOC2, and this increase was partially abolished by silencing FAK or LY290042. Furthermore, we found that general transcription factor 2I (GTF2I) was enriched at the promoter region of SMOC2 and that integrin β1 interacted with SMOC2 in BMP9-treated MEFs. Our findings demonstrate that SMOC2 can promote BMP9-induced osteogenic differentiation by enhancing the FAK/PI3K/AKT pathway, which may be triggered by facilitating the interaction between SMOC2 and integrin β1.

Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, non-coding RNAs (ncRNAs), proteins, cytokines, and lipids, and mediate intercellular signal transduction. Bone is a connective tissue with a nerve supply and high vascularization. The repair process after injury is highly complex, involving interactions among multiple cell types and biological signaling pathways. Bone regeneration consists of a series of coordinated osteoconductive and osteoinductive biological processes. As mediators of intercellular communication, EVs can promote bone regeneration by regulating osteoblast-mediated bone formation, osteoclast-mediated bone resorption, and other pathways. This review summarizes the biogenesis of EVs and the mechanisms by which EV-mediated intercellular communication promotes bone regeneration. Additionally, we focus on the research progress of EVs in various diseases related to bone regeneration. Finally, based on the above research, we explore the clinical applications of engineered EVs in the diagnosis and treatment of bone regeneration-related diseases.

Background. Standard posterior percutaneous endoscopic cervical discectomy (PECD) is considered an effective minimally invasive surgery. Although standard PECD can be used to treat radiculopathy with relatively minimal trauma, it is still a challenge to use this approach for treating myelopathy. Objective. This report is aimed at first describing a posterior transpedicular approach under endoscopy for myelopathy and evaluating the feasibility and short‐term clinical effects of this approach. Methods. In our retrospective analysis between Feb. 2016 to Mar. 2017, 16 patients managed with PECD using the posterior transpedicular approach for symptomatic single‐segment myelopathy. Surgery involved drilling 1/2 to 2/3 of the medial portion of the pedicle under endoscopy to provide sufficient space and an appropriate angle for inserting the endoscope into the spinal canal, followed by ventral decompression of the spinal cord. Computed tomography and magnetic resonance imaging were used to evaluate pedicle healing and spinal cord decompression. The primary outcomes included a visual analog scale (VAS) scores of axial neck pain and Japanese Orthopaedic Association (JOA) scores of neurological conditions. Results. All patients completed a 1‐year follow‐up examination. The mean duration of surgery was 95.44 ± 19.44 min (52–130 min). The fluoroscopy duration was 5.88 ± 1.05 (4–7). The VAS scores of axial pain significantly improved from 6.94 ± 0.75 preoperatively to 2.88 ± 1.22 postoperatively (P < 0.05). The mean JOA scores improved from 8.50 ± 1.12 preoperatively to 14.50 ± 1.46 at the final follow‐up (P < 0.05). The effects were excellent in 8 cases, good in 6 cases, and fair in 2 cases. After partial pedicle excision, the width of the remaining pedicle was 1.70 ± 0.22 mm postoperatively and significantly recovered to 3.38 ± 0.49 mm at the 1‐year follow‐up. There were no surgery‐related complications, such as dural tearing, spinal cord injury, nerve root injury, pedicle fracture, and cervical hematocele or infection. Conclusions. The posterior transpedicular approach is an effective method for the treatment of myelopathy in select patients and is a supplement to the described surgical approach for PECD.

Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.

Background: A series of full-endoscopic lumbar interbody fusions have been reported, but special fusion cages or operating instruments are often needed, and there are many complications in the operation and the learning curve is long. We have used a single portal endoscopic system for lumbar interbody fusion in a novel posterolateral transarticular approach, which will take advantage of the incision for pedicle screw insertion and avoid nerve root damage by using a transparent plastic working tube. The purpose of this study was to present the surgical technique of full endoscopic posterolateral transarticular lumbar interbody fusion (FE-PTLIF) and to analyze the preliminary clinical results.Methods: A total of 39 patients (17 men and 22 women; mean age [x̅ ± s] 55.2 ± 12.2 years) have been enrolled in this retrospective study between March 2019 and January 2021 in the Second Affiliated Hospital of Chongqing Medical University. All patients were treated with full endoscopic lumbar interbody fusion via posterolateral transarticular approach with a transparent plastic working tube. Demographic characteristics, diagnosis, operative time, and estimated blood loss were evaluated. Intraoperative photo and perioperative imaging were recorded. The preoperative and postoperative clinical data were collected for statistical analysis.Results: The preliminary clinical follow-up data achieved good results. No patients had serious postoperative complications and none of these patients required revision surgery during the perioperative or follow-up period. We compared the visual analogue scale and Oswestry disability index scores before and after surgery. The differences were statistically significant (P < 0.05). The mean total blood loss (including drainage blood) was 54.4 ± 20.3 ml. The mean operative time was 130.5 ± 23.8 min. At the last follow-up, the fusion rate of the lumbar intervertebral space was 100%.Conclusions: This novel posterolateral transarticular approach and transparent plastic working tube can reduce the difficulty of the operation, so that the conventional intervertebral fusion cage [bullet-shaped polyetheretherketone (PEEK) nonexpandable fusion cage] and surgical instruments can be used in the full endoscopic lumbar intervertebral fusion surgery, which can reduce the cost and improve the efficiency of the operation.