BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization Through PINK1/Parkin Signaling Pathway: Focus on Immune Responses in the Perichondrium

Dear Editor,

Recently, we read with great interest an article titled “BMSC-Derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization through PINK1/Parkin Signaling Pathway” published by Li et al. ¹ This article was brought to our attention as a result of an investigation into the role of macrophages in the development and healing of osteoarthritis (OA) through the regulation of inflammation. Recently, the role of immune cells in cartilage regeneration are highlighted and discussed in detail related the shift the M1/M2 macrophages polarization. ² Indeed, macrophages infiltrating the perichondrium are able to modulate the secretion and motility of chondrocytes. ³ However, the role of mast cells often remains undervalued. We aim to discuss the cell-cell interactions of mast cells and their impact on M2 polarization.

Inflammatory alterations of the perichondrium can have significant effects on both the structure and function of cartilage. The inflammatory responses typically involve the infiltration of macrophages and neutrophils, and their secretory activity to release pro-inflammatory cytokines. Mast cells are known to play a critical role in the polarization of macrophages to the M1 phenotype, as well as secrete of tryptases that mediate cartilage damage and proteolytic loss of aggrecan proteoglycans in arthritis. ⁴ These effects can lead to prolonged chronic inflammation, potentially compromising the structural integrity and function of cartilage. On the other hand, the involvement of mast cells in reducing inflammation and promoting M2 polarization through direct cell-cell interactions has recently been discovered, ⁵ demonstrating the dual role of these cells.

Inflammatory alterations in the perichondrium can profoundly affect cartilage health and function. However, the infiltration of mast cells can be seen not as a bad omen, but as a Trojan horse with undiscovered intentions. Understanding the underlying causes and mechanisms of this inflammation is critical to developing effective treatment strategies for preventing long-term insufficiency of cartilaginous tissues.