Platelet-rich plasma-derived exosomes attenuate intervertebral disc degeneration by promoting NLRP3 autophagic degradation in macrophages

• DOI: 10.1016/j.intimp.2022.108962
• Publication Date: 2022-06-24T00:24:22Z
• Authors: Jun Qian; Xiangdong Wang; Guanghui Su; Xiaolin Shu; Zucheng Huang; Huaji Jiang; Qingan Zhu
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Platelet-Rich Plasma; Macrophages; NLR Family, Pyrin Domain-Containing 3 Protein; Humans; Intervertebral Disc Degeneration; Exosomes; Intervertebral Disc; 3. Good health

Intervertebral disc degeneration (IDD) is a common orthopedic multifactorial disease associated with spine-related disorders, such as low back pain. Recent studies have shown that both platelet-rich plasma (PRP) and exosomes could be used to treat IDD, but the effects and mechanism of PRP-derived exosomes in the treatment of IDD are still unclear. This study showed that PRP-derived exosomes inhibited the polarization of M1 macrophages by regulating the NF-κB and MAPK pathways and affected the polarization of M2 macrophages by regulating STAT6 phosphorylation. Additionally, PRP-derived exosomes promoted the autophagic degradation of NLRP3 by increasing NLRP3 ubiquitination and reducing IL-1β and Caspase-1 production. Moreover, PRP-derived exosomes could reduce IL-1β-induced apoptosis of nucleus pulposus cells. Lastly, in vivo experiments confirmed that PRP-derived exosomes reduced the expression of inflammatory mediators and apoptotic factors, which could thereby alleviate the progression of IDD. Taken together, these data showed that PRP-derived exosomes could alleviate the IDD-associated inflammation by regulating the ubiquitination and autophagic degradation of NLRP3 inflammasome, providing new insights into the treatment of IDD.