Zongsheng Yin

Osteosarcoma (OS) is a highly aggressive malignant bone tumor predominantly affecting adolescents and children. Extracellular vesicles (EVs) significantly contribute to the progression of osteosarcoma by promoting intercellular communication via the transportation of biomolecules and activation of signaling pathways. However, the specific role of tenascin-C (TNC) transmitted by EVs in osteosarcoma remains poorly understood. In this study, we reanalyzed mass spectrometry data of osteosarcoma-derived EV proteins from public databases. EVs were isolated and characterized using standard protocols. The expression levels of EV-derived TNC (EVs-TNC) were measured by western blot or enzyme-linked immunosorbent assay. Functional assays were used to elucidate the role of EVs-TNC in promoting OS malignancy. Transcriptome sequencing was conducted to identify downstream effectors of EVs-TNC. Our results revealed elevated circulating EVs-TNC concentrations in OS patients versus healthy controls. Furthermore, EVs-TNC derived from OS cell lines (SJSA-1 and 143B) were internalized by MG-63 cells, enhancing their proliferative and migratory capabilities. Mechanistically, EVs-TNC was found to regulate angiotensin II receptor type 1 (AGTR1) expression, suggesting a potential signaling pathway involved in OS progression. This study highlights the role of EVs-TNC in promoting OS proliferation and migration, indicating that targeting EVs-TNC may offer a novel treatment strategy for osteosarcoma.

Young adults with comminuted femoral neck fractures face elevated risks of postoperative shortening and osteonecrosis of the femoral head (ONFH) This study evaluates a novel surgical protocol integrating the Femoral Neck System (FNS) and 3D-printed patient-specific Cannulated Compression Screw (CCS) navigation guides to address these challenges. A retrospective analysis was conducted on 75 young adults with femoral neck fractures complicated by posteromedial wall comminution/defects treated between October 2022 and June 2024. Patients were stratified into three groups: CCS fixation, FNS fixation, and FNS + CCS fixation. For the FNS + CCS group, preoperative 3D CT data were reconstructed in Mimics 21.0 software to establish fracture models, simulate reductions, and design patient-specific CCS navigation guides. Outcome measures included operative time, number of intraoperative fluoroscopies, fracture healing time, full weight-bearing time, follow-up duration, Garden alignment index, Harris Hip Score (HHS), femoral neck shortening, reduction quality, and ONFH incidence. Significant differences in operative time were observed between FNS and CCS groups (P < 0.01), and between FNS + CCS and CCS groups (P < 0.05). The FNS group demonstrated shorter full weight-bearing time than the CCS group but longer than the FNS + CCS group (P < 0.05). The number of intraoperative fluoroscopies was significantly lower in the FNS group than in both the CCS and FNS + CCS groups (P < 0.05). The FNS + CCS group exhibited superior HHS compared to the CCS group (P < 0.01) and significantly reduced femoral neck shortening versus the FNS group (P < 0.05). ONFH incidence was markedly lower in the FNS + CCS group than in both monotherapy groups (P < 0.05). No intergroup differences were detected in healing time, follow-up duration, Garden index, or reduction quality. The FNS-CCS combined fixation with patient-specific navigation guides effectively minimizes postoperative femoral neck shortening, accelerates functional recovery, and reduces ONFH incidence in young adults with comminuted femoral neck fractures, establishing a stable and controllable therapeutic protocol.

Chondrocyte senescence is a critical pathological hallmark of osteoarthritis (OA). Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging; however, the precise underlying mechanism remains elusive. Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression. SPI1 binds to the PERK promoter, thereby promoting its transcriptional activity. Importantly, PERK, rather than GCN2, facilitates eIF2α phosphorylation, activating the mitochondrial unfolded protein response (UPR^mt) and impeding chondrocyte senescence. Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPR^mt activation and accelerated OA progression. Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration. In summary, our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPR^mt signaling through PERK, which may present a novel therapeutic target for treating OA.

Percutaneous Endoscopic Transforaminal Discectomy (PETD) is recognized as the leading surgical intervention for lumbar disc herniation (LDH). Moreover, Body Mass Index (BMI) has been established as an independent risk factor for disc reherniation post-PETD. Furthermore, there is a lack of studies investigating the biomechanical changes in the disc post-PETD in relation to diverse BMI levels. A three-dimensional nonlinear finite element model was developed to simulate the L3-S1 lumbar spine, and a surgical model of the lumbar 4/5 right PETD was also constructed. Forces of 392 N (BMI 20.76 kg/m2), 457 N (24.22 kg/m2), 523 N (27.68 kg/m2), 588 N (31.14 kg/m2) and 653 N (34.6 kg/m2) were applied from the superior edge of the L3 vertebrae. The equivalent von Mises stresses and maximum deformation of the L4/5 nucleus pulposus were observed in normal group and PETD surgery group. We established normal and PETD surgery model with different BMIs, contributes to understand the equivalent von Mises stresses and maximum deformation of the L4/5 nucleus pulposus with different BMI. The results indicated that the rise in BMI correlates with heightened equivalent von Mises stresses and maximum deformation within the L4/5 nucleus pulposus in both in normal group and PETD surgery group. Besides, the von Mises stress and maximum deformation of the NP in flexion loading are significantly higher than in other loading conditions under the same BMI condition. These values, alongside the occurrence of high-stress areas, display fluctuations across distinct postures, under the influence of BMI. Furthermore, a discernible accumulation of stress was noted within the compromised regions of the nucleus pulposus. The study suggested that patients who undergone PETD surgery should refrain from engaging in strenuous activities especially flexion during early rehabilitation through finite element analysis. For patients with a high BMI, it is advisable to scientifically reduce weight before and after the surgery in order to maintain appropriate stress on the intervertebral disc.

Purpose: To study the effect of miR-150-5p on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), and further explore the relationship between its regulatory mechanism and irisin. Methods: We isolated mouse BMSCs, and induced osteogenic differentiation by osteogenic induction medium. Using qPCR to detect the expression of osteogenic differentiation-related genes, western blot to detect the expression of osteogenic differentiation-related proteins, and luciferase reporter system to verify that FNDC5 is the target of miR-150-5p. Irisin intraperitoneal injection to treat osteoporosis in mice constructed by subcutaneous injection of dexamethasone. Results: Up-regulation of miR-150-5p inhibited the proliferation of BMSCs, and decreased the content of osteocalcin, ALP activity, calcium deposition, the expression of osteogenic differentiation genes (Runx2, OSX, OCN, OPN, ALP and BMP2) and protein (BMP2, OCN, and Runx2). And down-regulation of miR-150-5p plays the opposite role of up-regulation of miR-150-5p on osteogenic differentiation of BMSCs. Results of luciferase reporter gene assay showed that FNDC5 gene was the target gene of miR-150-5p, and miR-150-5p inhibited the expression of FNDC5 in mouse BMSCs. The expression of osteogenic differentiation genes and protein, the content of osteocalcin, ALP activity and calcium deposition in BMSCs co-overexpressed by miR-150-5p and FNDC5 was significantly higher than that of miR-150-5p overexpressed alone. In addition, the overexpression of FNDC5 reversed the blocked of p38/MAPK pathway by the overexpression of miR-150-5p in BMSCs. Irisin, a protein encoded by FNDC5 gene, improved symptoms in osteoporosis mice through intraperitoneal injection, while the inhibitor of p38/MAPK pathway weakened this function of irisin. Conclusion: miR-150-5p inhibits the osteogenic differentiation of BMSCs by targeting irisin to regulate the/p38/MAPK signaling pathway, and miR-150-5p/irisin/p38 pathway is a potential target for treating osteoporosis.

Chromatin accessibility has been used to define how cells adopt region-specific neural fates. BAF45D is one of the subunits of a specialised chromatin remodelling BAF complex. It has been reported that BAF45D is expressed in spinal cord neural stem cells (NSCs) and regulates their fate specification. Within the developing vertebrate spinal cord, HOX genes exhibit spatially restricted expression patterns. However, the chromatin accessibility of BAF45D binding HOX genes in spinal cord NSCs is unclear. In the present study, we found that in H9-derived spinal cord NSCs, BAF45D targets TBX6, a gene that regulates spinal cord neural mesodermal progenitors. Furthermore, BAF45D binding to the NES gene is much more enriched in H9-derived spinal cord NSCs chromatin compared to ESCs chromatin. In addition, BAF45D binding to anterior and trunk/central HOX genes, but not to lumbosacral HOX genes, was much more enriched in NSCs chromatin compared to ESCs chromatin. These results may shed new light on the role of BAF45D in regulating region-specific spinal cord NSCs by targeting HOX genes.