![]() ![]() Studies have shown that immunity and inflammation play a significant role in the progression of IVDD, with different subtypes of immune cells contributing to this process. Despite ongoing studies, effective therapeutics for the retardation or reversal of IVDD are still lacking. IVDD is the underlying cause of low back pain, which affects over 80% of the global population. However, the accumulation of age, injury, and immune factors can negatively impact the IVD, leading to the IVD degeneration (IVDD). Its primary function is to support the stability of the spinal column. The intervertebral disc (IVD) is composed of the adjacent cartilaginous endplates (CEP), the surrounding annulus fibrosus (AF) and the inner nucleus pulposus (NP). In conclusion, our findings highlight the significant role of dNPc-exo in IVDD process and provide a basis for further investigation into the mechanism of IVDD and the potential of exosome-based therapy. We conducted experiments using rat model of IVDD and observed that the exosomes carrying miR-27a-3p actually induced the M1 polarization of macrophages and exacerbated the degradation of IVD. And then, we discovered that dNPc-exo has the ability to transport miR-27a-3p and target the PPARγ/NFκB/PI3K/AKT signaling pathway, thereby influencing the M1 polarization of macrophages. Notably, through RNA-sequencing analysis of dNPc-exo and nNPc-exo groups, we identified miR-27a-3p as a highly expressed miRNA in the dNPc-exo group, which significantly influences the induction of M1 polarization of macrophages. Additionally, we discovered that dNPc releases exosomes (dNPc-exo) could promote the polarization of macrophages towards the M1 phenotype. In this study, we observed an increase in the number of M1 macrophages as the intervertebral disc (IVD) degraded. Finally, an animal model of IVDD was utilized to investigate the impact of dNPc-exo on inducing M1 polarization of macrophages and its role in the IVDD process. Furthermore, western blot and qRT-PCR were employed to demonstrate the regulatory effect of microRNAs carried by dNPc-exo on downstream target signaling pathways in macrophages. RNA-sequencing analysis was conducted to examine the expression levels of microRNAs in the dNPc-exo and nNPc-exo groups, and qRT-PCR was performed to investigate the effect pf different microRNA to induce macrophage polarization. ![]() The M1 phenotype was assessed using western blot, flow cytometry, immunofluorescence staining, and qRT-PCR. Subsequently, exosomes derived from degenerated NP cells (dNPc-exo) and non-degenerated NP cells (nNPc-exo) were collected and co-cultured with M0 macrophages, which were induced from THP-1 cells. Immunohistochemistry analysis was performed to determine the number of M1 macrophages in NP tissue. Nucleus pulposus (NP) tissue and nucleus pulposus cells (NPc) were collected from patients with intervertebral disc degeneration (IVDD) and idiopathic scoliosis. This study aims to investigate the role of exosomes derived from degenerated nucleus pulposus (dNPc) in the process of macrophages M1 polarization. Exosomes (exo) are believed to play a significant role in intercellular communication. Previous studies have indicated that the infiltration of immunocytes, specifically macrophages, plays a crucial role in the advancement of IVDD. Intervertebral disc degeneration (IVDD) is a major contributor to spinal disorders. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |