Lumbar diseases have become a major problem affecting human health worldwide. Conservative treatment of lumbar diseases is difficult to achieve ideal results, and surgical treatment of trauma, complications, it is imperative to develop a new treatment method. This study aims to explore the regulatory mechanism of cartilage endplate ossification caused by abnormal stress, and design intervention targets for this mechanism, so as to provide theoretical reference for the prevention and treatment of lumbar degeneration. In vivo, we constructed spinal instability model in mice. In vitro, we used a mechanical tensile machine to simulate the abnormal stress conditions of the endplate cartilage cells. Through the high-throughput sequencing, we found the enrichment of Hippo signaling pathway. As YAP is a key protein in the Hippo signaling pathway, we then created cartilaginous YAP elimination mice (Col2::YAPfl/fl). The lumbar spine model was constructed again in these mice for H&E, SOFG and immunofluorescence staining. In vitro lentivirus was used to knock out YAP, immunofluorescence staining, WB and qPCR were performed. Finally, we conducted therapeutic experiments by using YAP agonist and AAV5 carrying YAP plasmids. We collected 8w samples from C57/BL6 mice after modeling. We found ossification of the endplate in mice similar to human disc degeneration. High-throughput sequencing of stretched cells demonstrated high enrichment of the Hippo signaling pathway. By immunofluorescence staining, it was confirmed that Col-II decreased and Col-X gradually increased in the endplate cartilage of mice. This was also confirmed at 7 days after an in vitro stretch of 5% and 12%. Meanwhile, we found that cartilaginous YAP elimination mice developed very severe endplate degeneration. However, the endplate was well protected by intraperitoneal injection of YAP agonist or AAV5-YAP endplate injection, and the results in vitro were consistent with that. In the process of cartilaginous ossification, abnormal stress regulates Col10a1 to promote cartilage endplate ossification through Hippo signaling pathway mediated YAP, and we expect to find potential drug targets for treatment through this mechanism

Spinal infections are rare diseases, whose management highlights the importance of a multidisciplinary approach. Although treatment is based on antibiotics, always selected on coltural and antibiogram tests, surgery is required in case of development of spinal instability or deformity, progressive neurological deficits, drainage of abscesses, or failure of medical treatment. The first step of the algorithm is diagnosis, that is established on MRI with contrast, PET/CT scan, blood tests (CRP and ESR) and CT-guided needle biopsy. Evaluation of response to the specific antibiotic therapy is based on variations in Maximum Standardized Uptake Value (SUVmax) after 2 to 4 weeks of treatment. In selected cases, early minimally invasive surgery was proposed to provide immediate stability and avoid bed-rest. From 1997 to 2014, 182 patients affected by spinal infections have been treated at the same Institution (Istituto Ortopedico Rizzoli – Bologna, Italy) according to the proposed algorithm. Mean age was 56 years (range 1 – 88). Male to female ratio was 1.46. Minimum follow-up was 1 year. Infections were mostly located in the lumbar spine (57%) followed by thoracic (37%) and cervical spine (6%). Conservative treatment based on antibiotics needed surgery (open and/or percuteneous minimally invasive) as an adjuvant in 83 patients out of 182 (46%). Management of spinal infections still remains a challenge in spinal surgery and a multisciplinary approach is mandatory. This algorithm represents the shared decision- making process from diagnosis to the most appropriate treatment and it led to successful outcomes with a low-complication rate. We present this algorithm developed to organize the various professionals involved (orthopaedic surgeons, nuclear medicine and infective disease specialists, interventional radiologists and anaestesiologists) and set a shared pathway of decision making in order to uniform the management of this complex disease

Summary Statement. Burst fractures were simulated in vitro on human cadaveric spine segments. Displacement of the facet joints and pedicles were measured throughout the fracture process showing how these bony structures behave when an impact load is delivered. Introduction. Burst fractures account for almost 30% of all spinal injuries, which may result in severe neurological deficit, spinal instability and hence life impairment. 1. The onset of the fracture is usually traumatic, caused by a high-energy impact loading. Comminution of the endplates and vertebral body, retropulsion of fragments within the canal and increase of the intrapedicular distance are typical indicators of the injury. Experimental and numerical studies have reported strain concentration at the base of the pedicles, suggesting that the posterior processes play a fundamental role in the fracture initiation. 2,3. However, little is known about the dynamic behaviour of the vertebra undergoing an impact load. The aim of this study was to provide an in vitro cadaveric investigation on burst fracture, focusing on the widening of the facet joints and pedicles during the fracture development. Methods. Eight three-adjacent-vertebrae segments (T9-T10-T11, T12-L1-L2, L3-L4-L5) were harvested from three human spines preserving the ligaments and intervertebral discs. A testing frame was designed to hold the sample whilst undergoing an axial impact load (delivered through a drop-weight rig). Lateral displacement was recorded by two transducers (LVDT) sampled at 5000 Hz and data were used to calculate the percent maximum dynamic widening (MW) and percent residual widening after the impact (RW). LVDTs were positioned in contact with the most lateral region of the cranial facet joints where the central vertebra was lumbar; or posteriorly to the base of the pedicles for thoracic. Samples were divided into two groups to achieve two different grade of severity of the fracture by delivering two different amount of energy: High (HE) and Low (LE). Samples underwent HR-pQCT scanning prior and after fracturing to assess percent canal narrowing (CN), intrapedicular distance and grade the fracture. Differences between results were assessed using Mann-Whitney U test. Results. Burst fractures were induced in all the samples (fragment retropulsion was present in all HE samples). The median energy delivered to each group was 206J (HE) and 148J (LE) which led to a significant difference in the median CN (HE: 32.4%; LE: 11.8%; p=0.029). No significant difference was found between HE and LE in terms of MW (p=0.11), or RW (p=0.85). Furthermore, MW and CN were poorly correlated (R. 2. =0.13). In all the cases, the first peak in the widening data coincided with MW (median 12.8%, range 4.3–21.8%). RW measurements (median 2.8%, range −1.3–11.5%) were validated against HR-pQCT scans showing excellent agreement (R. 2. =0.93). Discussion/Conclusion. Results from this study provided further insight on the burst fracture process supporting the wedging effect of the adjacent facet joints when the impact load is transmitted. Indeed, the pedicles were forced to widen up to a critical value (MW), after which they fractured. Further experiments will help clarifying the influence of the amount of energy delivered