Mesenchymal stem cells and their extracellular vesicles in bone and joint diseases: targeting the NLRP3 inflammasome.

ABSTRACT

The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a cytosolic multi-subunit protein complex, and recent studies have demonstrated the vital role of the NLRP3 inflammasome in the pathological and physiological conditions, which cleaves gasdermin D to induce inflammatory cell death called pyroptosis and mediates the release of interleukin-1 beta and interleukin-18 in response to microbial infection or cellular injury. Over-activation of the NLRP3 inflammasome is associated with the pathogenesis of many disorders affecting bone and joints, including gouty arthritis, osteoarthritis, rheumatoid arthritis, osteoporosis, and periodontitis. Moreover, mesenchymal stem cells (MSCs) have been discovered to facilitate the inhibition of NLRP3 and maybe ideal for treating bone and joint diseases. In this review, we implicate the structure and activation of the NLRP3 inflammasome along with the detail on the involvement of NLRP3 inflammasome in bone and joint diseases pathology. In addition, we focused on MSCs and MSC-extracellular vesicles targeting NLRP3 inflammasomes in bone and joint diseases. Finally, the existing problems and future direction are also discussed.