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Abstract Background Adjacent segment disease (ASD) is a common and serious complication that can develop in the mid- to long-term after lumbar fusion surgery. However, the underlying mechanisms of ASD are not yet fully understood. This study aimed to develop and validate a risk prediction model for ASD in patients who underwent transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative diseases. Methods Patients with lumbar degenerative disease who underwent TLIF between January 2015 and December 2016 were included in the retrospective study. The participants were divided into two groups: ASD and non-ASD. Univariate and multivariate logistic regression analyses were performed to identify factors influencing ASD after TLIF surgery. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the model’s discrimination, calibration and clinical value, respectively. Results A total of 11.5% (59/513) of patients developed ASD. Higher BMI, lower BMD, higher disc grade, and reduced disc height were identified as independent risk factors for ASD after TLIF. The model demonstrated good discrimination in both the training and validation sets, with calibration and Hosmer-Lemeshow tests confirming accuracy, and DCA demonstrating clinical applicability. Conclusions The nomogram model demonstrated promise in predicting ASD in patients who underwent TLIF, aiding clinicians in selecting the most suitable surgical approach and optimizing surgical decisions.

Abstract Intervertebral disc degeneration (IDD) is a major cause of discogenic pain, and is attributed to the dysfunction of nucleus pulposus, annulus fibrosus, and cartilaginous endplate (CEP). Osteopontin (OPN), a glycoprotein, is highly expressed in the CEP. However, little is known on how OPN regulates CEP homeostasis and degeneration, contributing to the pathogenesis of IDD. Here, we investigate the roles of OPN in CEP degeneration in a mouse IDD model induced by lumbar spine instability and its impact on the degeneration of endplate chondrocytes (EPCs) under pathological conditions. OPN is mainly expressed in the CEP and decreases with degeneration in mice and human patients with severe IDD. Conditional Spp1 knockout in EPCs of adult mice enhances age-related CEP degeneration and accelerates CEP remodeling during IDD. Mechanistically, OPN deficiency increases CCL2 and CCL5 production in EPCs to recruit macrophages and enhances the activation of NLRP3 inflammasome and NF-κB signaling by facilitating assembly of IRAK1-TRAF6 complex, deteriorating CEP degeneration in a spatiotemporal pattern. More importantly, pharmacological inhibition of the NF-κB/NLRP3 axis attenuates CEP degeneration in OPN-deficient IDD mice. Overall, this study highlights the importance of OPN in maintaining CEP and disc homeostasis, and proposes a promising therapeutic strategy for IDD by targeting the NF-κB/NLRP3 axis.

Low back pain, mainly caused by intervertebral disc degeneration (IVDD), is a common health problem; however, current surgical treatments are less than satisfactory. Thus, it is essential to develop novel non-invasive surgical methods for IVDD treatment. Here, we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage (ECM-Gels) that are loaded with cartilage endplate stem cells (CESCs). After loaded with CESCs overexpressing Sphk2 (Lenti-Sphk2-CESCs) and injected near the cartilage endplate (CEP) of rats in vivo, ECM-Gels produced Sphk2-engineered exosomes (Lenti-Sphk2-Exos). These exosomes penetrated the annulus fibrosus (AF) and transported Sphk2 into the nucleus pulposus cells (NPCs). Sphk2 activated the phosphatidylinositol 3-kinase (PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs, ultimately ameliorating IVDD. This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes.

Recognizing students’ behaviors in classes based on videos of their activity plays an important role in improving teaching quality and paying attention to the healthy growth of students. The existing student behavior recognition methods mainly focus on the behavior of the single student and have low performance and efficiency. To recognize the behaviors of multiple students in the classroom at the same time, we propose a fast and effective solution, called ET-YOLOv5s, which is an improved YOLOv5s with ESRGAN (Enhanced Super-Resolution Generative Adversarial Network) and a tiny object detection module in this paper. First, the ESRGAN is adopted to generate high-definition images from original images of real classroom environments in colleges to improve the recognition accuracy. Then a tiny object detection module is added to the YOLOv5s to detect the smaller objects on high-definition images, such as phones, books, and students sitting at the back of the classroom. Finally, the experimental results show that the proposed solution can detect 11 kinds of students’ behaviors in classrooms, including playing mobile phones, having class, sitting with hands on face, sitting turn right, sitting turn left, bowing, sleeping, and so on. Compared with YOLOv4, YOLOv5s, and other tiny target detection algorithms, it has better detection performance and can effectively deal with the behavior recognition of multiple students.

Purpose To evaluate the vertebral bone mineral density and the value of stand-alone oblique lumbar interbody fusion (SA OLIF) for the management of single-level adjacent segment disease (ASD) and primary lumbar degenerative diseases. Patients and methods Seventy-eight patients undergoing single-level SA OLIF was divided into index surgery group ( n = 36) or revision surgery group ( n = 42) at single center. The vertebral body Hounsfield units (HU) value was measured to assess bone mineral density of operated level by the preoperative CT. The following data were retrospectively collected and compared between the two groups: demographic, surgical data, clinical results, and complications. Results No differences were found between the two groups in surgical data. The fusion segment HU values in the revision group were significantly higher than that in the index group (147.4 ± 35.3 vs 129.2 ± 38.4 p = .033). There were significant differences while comparing fusion segment HU values to L1–L4 horizontal plane (147.4 ± 35.3 vs 126.1 ± 28.4, p = .000) and L1 (147.4 ± 35.3 vs 126.8 ± 26.2, p = .000) in revision group, meanwhile, no statistically significant difference was observed in index group ( p > .05). The cage subsidence was observed in the revision group ( n = 2) and index group ( n = 9) ( p = .045). The patients with cage subsidence had significantly lower vertebral HU values. Conclusion SA OLIF is valid alternative to the traditional posterior approach in the management of ASD with good clinical outcomes at short-term follow-up. Increased HU values of fusion segment may play a role in the management of ASD by SA OLIF.

Abstract Background The degenerative disc disease (DDD) is a major cause of low back pain. The physiological low-glucose microenvironment of the cartilage endplate (CEP) is disrupted in DDD. Glucose influences protein O-GlcNAcylation via the hexosamine biosynthetic pathway (HBP), which is the key to stem cell fate. Thiamet-G is an inhibitor of O-GlcNAcase for accumulating O-GlcNAcylated proteins while 6-diazo-5-oxo-l-norleucine (DON) inhibits HBP. Mechanisms of DDD are incompletely understood but include CEP degeneration and calcification. We aimed to identify the molecular mechanisms of glucose in CEP calcification in DDD. Methods We assessed normal and degenerated CEP tissues from patients, and the effects of chondrogenesis and osteogenesis of the CEP were determined by western blot and immunohistochemical staining. Cartilage endplate stem cells (CESCs) were induced with low-, normal-, and high-glucose medium for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. CESCs were induced with low-glucose and high-glucose medium with or without Thiamet-G or DON for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. Sox9 and Runx2 O-GlcNAcylation were measured by immunofluorescence. The effects of O-GlcNAcylation on the downstream genes of Sox9 and Runx2 were determined by Q-PCR and western blot. Results Degenerated CEPs from DDD patients lost chondrogenesis, acquired osteogenesis, and had higher protein O-GlcNAcylation level compared to normal CEPs from LVF patients. CESC chondrogenic differentiation gradually decreased while osteogenic differentiation gradually increased from low- to high-glucose differentiation medium. Furthermore, Thiamet-G promoted CESC osteogenic differentiation and inhibited chondrogenic differentiation in low-glucose differentiation medium; however, DON acted opposite role in high-glucose differentiation medium. Interestingly, we found that Sox9 and Runx2 were O-GlcNAcylated in differentiated CESCs. Finally, O-GlcNAcylation of Sox9 and Runx2 decreased chondrogenesis and increased osteogenesis in CESCs. Conclusions Our findings demonstrate the effect of glucose concentration on regulating the chondrogenic and osteogenic differentiation potential of CESCs and provide insight into the mechanism of how glucose concentration regulates Sox9 and Runx2 O-GlcNAcylation to affect the differentiation of CESCs, which may represent a target for CEP degeneration therapy.

Stem cells derived from cartilage endplate (CEP) cells (CESCs) repair intervertebral disc (IVD) injury; however, the mechanism remains unclear. Here, we evaluated whether CESCs could transdifferentiate into nucleus pulposus cells (NPCs) via autocrine exosomes and subsequently inhibit IVD degeneration. Exosomes derived from CESCs (CESC-Exos) were extracted and identified by ultra-high-speed centrifugation and transmission electron microscopy. The effects of exosomes on the invasion, migration, and differentiation of CESCs were assessed. The exosome-activating hypoxia-inducible factor (HIF)-1α/Wnt pathway was investigated using lenti-HIF-1α and Wnt agonists/inhibitors in cells and gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis in normal and degenerated human CEP tissue. The effects of GATA binding protein 4 (GATA4) on transforming growth factor (TGF)-β expression and on the invasion, migration, and transdifferentiation of CESCs were investigated using lenti-GATA4, TGF-β agonists, and inhibitors. Additionally, IVD repair was investigated by injecting CESCs overexpressing GATA4 into rats. The results indicated that CESC-Exos promoted the invasion, migration, and differentiation of CESCs by autocrine exosomes via the HIF-1α/Wnt pathway. Additionally, increased HIF-1α enhanced the activation of Wnt signaling and activated GATA4 expression. GATA4 effectively promoted TGF-β secretion and enhanced the invasion, migration, and transdifferentiation of CESCs into NPCs, resulting in promotion of rat IVD repair. CESCs were also converted into NPCs as endplate degeneration progressed in human samples. Overall, we found that CESC-Exos activated HIF-1α/Wnt signaling via autocrine mechanisms to increase the expression of GATA4 and TGF-β1, thereby promoting the migration of CESCs into the IVD and the transformation of CESCs into NPCs and inhibiting IVDD.

Abstract Background Radiotherapy to cancer patients is inevitably accompanied by normal tissue injury, and the bone is one of the most commonly damaged tissues. Damage to bone marrow mesenchymal stem cells (BM-MSCs) induced by radiation is thought to be a major cause of radiation-induced bone loss. Exosomes exhibit great therapeutic potential in the treatment of osteoporosis, but whether exosomes are involved in radiation-induced bone loss has not been thoroughly elucidated to date. The main purpose of this study is to investigate the role of exosomes derived from BM-MSCs in restoring recipient BM-MSC function and alleviating radiation-induced bone loss. Methods BM-MSC-derived exosomes were intravenously injected to rats immediately after irradiation. After 28 days, the left tibiae were harvested for micro-CT and histomorphometric analysis. The effects of exosomes on antioxidant capacity, DNA damage repair, proliferation, and cell senescence of recipient BM-MSCs were determined. Osteogenic and adipogenic differentiation assays were used to detect the effects of exosomes on the differentiation potential of recipient BM-MSCs, and related genes were measured by qRT-PCR and Western blot analysis. β-Catenin expression was detected at histological and cytological levels. Results BM-MSC-derived exosomes can attenuate radiation-induced bone loss in a rat model that is similar to mesenchymal stem cell transplantation. Exosome-treated BM-MSCs exhibit reduced oxidative stress, accelerated DNA damage repair, and reduced proliferation inhibition and cell senescence-associate protein expression compared with BM-MSCs that exclusively received irradiation. Following irradiation, exosomes promote β-catenin expression in BM-MSCs and restore the balance between adipogenic and osteogenic differentiation. Conclusions Our findings indicate that BM-MSC-derived exosomes take effects by restoring the function of recipient BM-MSCs. Therefore, exosomes may represent a promising cell-free therapeutic approach for the treatment of radiation-induced bone loss.

Degenerative cartilage endplate (CEP) shows decreased chondrification and increased ossification. Cartilage endplate stem cells (CESCs), with the capacity for chondro-osteogenic differentiation, are responsible for CEP restoration. CEP is avascular and hypoxic, while the physiological hypoxia is disrupted in the degenerated CEP. Hypoxia promoted chondrogenesis but inhibited osteogenesis in CESCs. This tissue-specific differentiation fate of CESCs in response to hypoxia was physiologically significant with regard to CEP maintaining chondrification and refusing ossification. MIF, a downstream target of HIF1A, is involved in cartilage and bone metabolisms, although little is known about its regulatory role in differentiation. In CESCs, MIF was identified as a key point through which HIF1A regulated the chondro-osteogenic differentiation. Unexpectedly, unlike the traditionally recognized mode, increased nuclear-expressed MIF under hypoxia was identified to act as a transcriptional regulator by interacting with the promoter of SOX9 and RUNX2. This mode of HIF1A/MIF function may represent a target for CEP degeneration therapy.

The original article [1] contains an error in Fig. 5 whereby sub-Fig. 5c, d & 5e are mistakenly mixed-up.

Degeneration of the cartilage endplate (CEP) induces intervertebral disc degeneration (IVDD). Nucleus pulposus cell (NPC) apoptosis is also an important exacerbating factor in IVDD, but the cascade mechanism in IVDD is not clear. We investigated the apoptosis of NPCs and IVDD when stimulated by normal cartilage endplate stem cell (CESC)- derived exosomes (N-Exos) and degenerated CESC-derived exosomes (D-Exos) in vitro and in vivo. Tert-butyl hydroperoxide (TBHP) was used to induce inflammation of CESCs. The bioinformatics differences between N-Exos and D-Exos were analyzed using mass spectrometry, heat map, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. NPC apoptosis was examined using TUNEL staining. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, Western blotting, and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in rats with IVDD. TBHP effectively induced inflammation and the degeneration of CEP in rat. NExos were more conducive to autophagy activation than D-Exos. The apoptotic rate of NPCs decreased obviously after treatment with N-Exos compared to D-Exos. N-Exos inhibited NPCs apoptosis and attenuated IVDD in rat via activation of the AKT and autophagy pathways. These results are the first findings to confirm that CEP delayed the progression of IVDD via exosomes. The therapeutic effects of N-Exos on NPC apoptosis inhibition and the slowing of IVDD progression were more effective than D-Exos due to activation of the PI3K/AKT/autophagy pathway, which explained the increase in the incidence of IVDD after inflammation of the CEP. [ABSTRACT FROM AUTHOR]