arXiv subjects

Zhaojie Wang

Publications and source records attributed to Zhaojie Wang.

2 recordsLinked to original sources

arXiv2023

Low-intensity pulsed ultrasound promotes mesenchymal stem cell transplantation-based articular cartilage regeneration via inhibiting the TNF signaling pathway

Background: Mesenchymal stem cell (MSC) transplantation therapy is highly investigated for the regenerative repair of cartilage defects. Low-intensity pulsed ultrasound (LIPUS) has the potential to promote chondrogenic differentiation of MSCs. However, its underlying mechanism remains unclear. Here, we investigated the promoting effects and mechanisms underlying LIPUS stimulation on the chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further evaluated its regenerative application value in articular cartilage defects in rats. Methods: LIPUS was applied to stimulate cultured hUC-MSCs and C28/I2 cells in vitro. Immunofluorescence staining, qPCR analysis, and transcriptome sequencing were used to detect mature cartilage-related markers of gene and protein expression for a comprehensive evaluation of differentiation. Injured articular cartilage rat models were established for further hUC-MSC transplantation and LIPUS stimulation in vivo. Histopathology and H&E staining were used to evaluate the repair effects of the injured articular cartilage with LIPUS stimulation. Results: The results showed that LIPUS stimulation with specific parameters effectively promoted the expression of mature cartilage-related genes and proteins, inhibited TNF-α gene expression in hUC-MSCs, and exhibited anti-inflammation in C28/I2 cells. In addition, the articular cartilage defects of rats were significantly repaired after hUC-MSC transplantation and LIPUS stimulation. Conclusions: Taken together, LIPUS stimulation could realize articular cartilage regeneration based on hUC-MSC transplantation due to the inhibition of the TNF signaling pathway, which is of clinical value for the relief of osteoarthritis.

physics.med-ph↗

arXiv2022

Unresolved excess accumulation of myelin-derived cholesterol contributes to scar formation after spinal cord injury

Background: Spinal cord injury triggers complex pathological cascades, resulting in destructive tissue damage and incomplete tissue repair. Scar formation is generally considered as a barrier for regeneration in central nervous system (CNS), while the intrinsic mechanism of scar-forming after spinal cord injury has not been completed deciphered. Methods: We assessed cholesterol hemostasis in spinal cord lesions and injured peripheral nerves using confocal reflection microscopy and real-time PCR analyses. The involvement of the proteins, which were predicted to promote cholesterol efflux in spinal cord lesions, were assessed with Liver X receptor (LXR) agonist and Apolipoprotein E (APOE) deficiency. The role of reverse cholesterol transport (RCT) in cholesterol clearance was examined in APOE KO mice injured sciatic nerves and myelin-overloaded macrophages in vitro. Finally, we determined the consequence of excess cholesterol accumulation in CNS by transplantation of myelin into neonatal spinal cord lesions. Results: We found that excess cholesterol accumulates in phagocytes and is inefficiently removed in spinal cord lesions in young-adult mice. Interestingly, we observed that excessive cholesterol also accumulates in injured peripheral nerves, but is subsequently removed by RCT. Meanwhile, preventing RCT led to macrophage accumulation and fibrosis in injured peripheral nerves. Furthermore, the neonatal mouse spinal cord lesions are devoid of myelin-derived lipids, and able to heal without excess cholesterol accumulation. We found that transplantation of myelin into neonatal lesions disrupts healing with excessive cholesterol accumulation, persistent macrophage activation and fibrosis, indicating myelin-derived cholesterol plays a critical role in impaired wound healing.

q-bio.TO↗