Osteoimmune Interactions and Therapeutic Potential of Macrophage-Derived Small Extracellular Vesicles in Bone-Related Diseases

Abstract

Due to the aging of the global population, the burden of bone-related diseases has increased sharply. Macrophage, as indispensable components of both innate immune responses and adaptive immunity, plays a considerable role in maintaining bone homeostasis and promoting bone establishment. Small extracellular vesicles (sEVs) have attracted increasing attention because they participate in cell cross-talk in pathological environments and can serve as drug delivery systems. In recent years, an increasing number of studies have expanded our knowledge about the effects of macrophage-derived sEVs (M-sEVs) in bone diseases via different forms of polarization and their biological functions. In this review, we comprehensively describe on the application and mechanisms of M-sEVs in various bone diseases and drug delivery, which may provide new perspectives for treating and diagnosing human bone disorders, especially osteoporosis, arthritis, osteolysis, and bone defects.

The Function and Mechanism of Anti-Inflammatory Factor Metrnl Prevents the Progression of Inflammatory-Mediated Pathological Bone Osteolytic Diseases

“…38,39 Immune inflammation and overexpression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) are associated with bone health issues, which have destructive impact on normal bone homeostasis through various mechanisms. 40 Catabolic states associated with immune inflammation and pathological bone loss are exemplified in a range of skeletal disorders, including periprosthetic osteolysis, 3,41 aseptic loosening, 42,43 osteoporosis, and rheumatoid arthritis. These conditions are major contributors to disability and impose a significant financial burden globally (Figure 1).…”

“…It stands as the primary cause for revision procedures. 40 The loosening of joint implants due to wear debris incurs a significant need for revision surgery, leading to severe complications and substantial economic burden. 69 The release of wear particles from the prosthetic materials triggers a persistent local inflammatory response, and inflammatory factors such as IL-1β, IL-6, TNF-α, RANKL and PGE2 were generated and secreted by macrophages, thereby stimulating osteoclast activities and resulting in bone loss around the implant.…”