Long noncoding RNA HCG18 inhibits the differentiation of human bone marrow-derived mesenchymal stem cells in osteoporosis by targeting miR-30a-5p/NOTCH1 axis.

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (LncRNAs) can influence bone cell differentiation and formation. However, it is unclear whether lncRNA HCG18 is involved in osteoporosis (OP). This study was conducted to investigate the regulation of HCG18 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated and cultured from mouse pathological models and osteoporosis patients. RT-qPCR was performed to detect the expression of HCG18 and miR-30a-5p in BMSCs. The interaction between HCG18 and miR-30a-5p was analyzed by dual luciferase assay and RNA pulldown assay. The interaction between miR-30a-5p and NOTCH1 3'-UTR was analyzed by dual luciferase assay. RT-qPCR and Western blotting were used to detect the expression of osteogenic genes Runx2, OCN and OPN. Hindlimb-unloaded (HU) mice model was established, and HCG18 was knocked down on bone-formation surfaces by using lentivirus mediated shRNA transfection. RESULTS: The expression of HCG18 was increased in BMSCs of OP patients, while the expression of miR-30a-5p was decreased. The expression of HCG18 and miR-30a-5p was negatively correlated in BMSCs. During the differentiation from BMSCs to osteoblasts, the expression of HCG18 was significantly downregulated, and the expression of miR-30a-5p was significantly upregulated. Overexpression of HCG18 was able to reverse the osteogenic-induced upregulation of miR-30a-5p expression, and knockdown of HCG18 further promoted the expression of miR-30a-5p. In addition, miR-30a-5p partially abolished the effect of HCG18 on osteogenic differentiation of BMSCs. NOTCH1 was a target protein of miR-30a-5p, and upregulation of NOTCH1 reversed the effect of miR-30a-5p on osteogenic differentiation of BMSCs. Furthermore, this study found that lentivirus mediated HCG18 knockdown on the bone-formation surfaces of hindlimb-unloaded (HU) mice partially alleviated unloading-induced bone loss CONCLUSIONS: HCG18 inhibited osteogenic differentiation of BMSCs induced by OP via the miR-30a-5p/NOTCH1 axis. HCG18 can be identified as a regulator of osteogenic differentiation of BMSCs.

Recent advances in nanomaterials for the treatment of spinal cord injury.

Spinal cord injuries (SCIs) are devastating. In SCIs, a powerful traumatic force impacting the spinal cord results in the permanent loss of nerve function below the injury level, leaving the patient paralyzed and wheelchair-bound for the remainder of his/her life. Unfortunately, clinical treatment that depends on surgical decompression appears to be unable to handle damaged nerves, and high-dose methylprednisolone-based therapy is also associated with problems, such as infection, gastrointestinal bleeding, femoral head necrosis, obesity, and hyperglycemia. Nanomaterials have opened new avenues for SCI treatment. Among them, performance-based nanomaterials derived from a variety of materials facilitate improvements in the microenvironment of traumatic injury and, in some cases, promote neuron regeneration. Nanoparticulate drug delivery systems enable the optimization of drug effects and drug bioavailability, thus contributing to the development of novel treatments. The improved efficiency and accuracy of gene delivery will also benefit the exploration of SCI mechanisms and the understanding of key genes and signaling pathways. Herein, we reviewed different types of nanomaterials applied to the treatment of SCI and summarized their functions and advantages to provide new perspectives for future clinical therapies.

Finite Element Analysis of a New Type of Spinal Protection Device for the Prevention and Treatment of Osteoporotic Vertebral Compression Fractures.

OBJECTIVE: To study the effectiveness of a new spinal protection device for preventing and treating osteoporotic vertebral compression fractures (OVCFs) by finite element analysis (FEA). METHODS: One healthy volunteer and one patient with 1-segment lumbar vertebral compression fractures were included in this experimental study. The DICOM files of two different lumbar spiral computed tomography (CT) scans were converted into STL files, and 3D finite element models of the lumbar spine were generated for normal and L1 vertebral fracture spines. A new type of spinal protection device was applied to reduce the stress on the anterior vertebral edge and direct the center of gravity posteriorly. The stress distribution characteristics of different finite element models of the lumbar spine were analyzed, revealing the characteristics of the stress distributed along the spine under the action of the new spinal protection device. RESULTS: Under normal conditions, the stress was mainly distributed in the middle and posterior columns of the spine. When the anterior border of the L1 vertebral body was fractured and collapsed, the stress distribution shifted toward the anterior column due to the center of gravity being directed forward. According to finite element analysis of the spine with the new protection device, the stress in the middle and posterior columns tended to increase, and that in the anterior column decreased. After the new type of spinal fixation device was applied, the stress at the L1 and L2 vertebral endplates decreased to a certain extent, especially that at the L1 vertebral body. The maximum stress on the L1 vertebral body decreased by 20% after the auxiliary device was applied. CONCLUSIONS: According to the FEA results, the new spinal protection device can effectively prevent and treat osteoporotic vertebral compression fractures (OVCFs), and can alter the stress distribution in the spine and reduce the stress in the anterior column of the vertebral body, especially in vertebral compression fractures.

Animal Models for Postoperative Implant-Related Spinal Infection.

Postoperative infections following implant-related spinal surgery are severe and disastrous complications for both orthopaedic surgeons and patients worldwide. They can cause neurological damage, disability, and death. To better understand the mechanism of these destructive complications and intervene in the process, further research is needed. Therefore, there is an urgent need for efficient, accurate, and easily available animal models to study the pathogenesis of spinal infections and develop new and effective anti-bacterial methods. In this paper, we provide a general review of the commonly used animal models of postoperative implant-related spinal infections, describe their advantages and disadvantages, and highlight the significance of correctly choosing the model according to the infection aspect under investigation. These models are valuable tools contributing to the better understanding of postoperative spinal infections and will continue to facilitate the invention of novel preventative and treatment strategies for patients with postoperative spinal infections. However, although they are valid and reproducible in some respects, the current animal models present certain limitations. Future ideal spinal infection animal models may assess the bacterial load of the same animal in real-time in vivo, and better mimic the human anatomy as well as surgical techniques. Strains other than Staphylococcus aureus account for a large proportion of postoperative spinal infections, and thus, the establishment of models to evaluate other types of microbial infections is expected in the future. Furthermore, novel transgenic models established on advancements in genome editing are also likely to be developed in the future.

The role of IL-1ß and TNF-α in intervertebral disc degeneration.

Low back pain (LBP), a prevalent and costly disease around the world, is predominantly caused by intervertebral disc (IVD) degeneration (IDD). LBP also presents a substantial burden to public health and the economy. IDD is mainly caused by aging, trauma, genetic susceptibility, and other factors. It is closely associated with changes in tissue structure and function, including progressive destruction of the extracellular matrix (ECM), enhanced senescence, disc cell death, and impairment of tissue biomechanical function. The inflammatory process, exacerbated by cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), are considered to be the key mediators of IDD and LBP. IL-1ß and TNF-α are the most important proinflammatory cytokines, as they have powerful proinflammatory activities and can promote the secretion of a variety of proinflammatory mediators. They are also upregulated in the degenerative IVDs, and they are closely related to various pathological IDD processes, including inflammatory response, matrix destruction, cellular senescence, autophagy, apoptosis, pyroptosis, and proliferation. Therefore, anti-IL-1ß and anti-TNF-α therapies may have the potential to alleviate disc degeneration and LBP. In this paper, we reviewed the expression pattern and signal transduction pathways of IL-1ß and TNF-α, and we primarily focused on their similar and different roles in IDD. Because IL-1ß and TNF-α inhibition have the potential to alleviate IDD, an in-depth understanding of the role of IL-1ß and TNF-α in IDD will benefit the development of new treatment methods for disc degeneration with IL-1ß and TNF-α at the core.