Phenotypic alteration of macrophages during osteoarthritis: a systematic review

Abstract

Objective Osteoarthritis (OA) has long been regarded as a disease of cartilage degeneration, whereas mounting evidence implies that low-grade inflammation contributes to OA. Among inflammatory cells involved, macrophages play a crucial role and are mediated by the local microenvironment to exhibit different phenotypes and polarization states. Therefore, we conducted a systematic review to uncover the phenotypic alterations of macrophages during OA and summarized the potential therapeutic interventions via modulating macrophages. Methods A systematic review of multiple databases (PubMed, Web of Science, ScienceDirect, Medline) was performed up to February 29, 2020. Included articles were discussed and evaluated by two independent reviewers. Relevant information was analyzed with a standardized and well-designed template. Results A total of 28 studies were included. Results were subcategorized into two sections depending on sources from human tissue/cell-based studies (12 studies) and animal experiments (16 studies). The overall observation indicated that M1 macrophages elevated in both synovium and circulation during OA development, along with lower numbers of M2 macrophages. The detailed alterations of macrophages in both synovium and circulation were listed and analyzed. Furthermore, interventions against OA via regulating macrophages in animal models were highlighted. Conclusion This study emphasized the importance of the phenotypic alterations of macrophages in OA development. The classical phenotypic subcategory of M1 and M2 macrophages was questionable due to controversial and conflicting results. Therefore, further efforts are needed to categorize macrophages in an exhaustive manner and to use advanced technologies to identify the individual roles of each subtype of macrophages in OA.

Proteoglycan-4 is an essential regulator of synovial macrophage polarization and inflammatory macrophage joint infiltration

“…It is clear that the dichotomous nature of M1–M2 macrophage polarization is insufficient to adequately describe the multifaceted and complex functions of macrophages in the synovium [ 49 ]. However, it remains useful to investigate changes in the phenotypic balance of macrophages according to the broad M1–M2 classification, especially if they can be correlated to structural and pathological changes at the tissue level.…”

“…However, it remains useful to investigate changes in the phenotypic balance of macrophages according to the broad M1–M2 classification, especially if they can be correlated to structural and pathological changes at the tissue level. We have selected two markers for M1 and M2 macrophages that have been used to study macrophage phenotypic balance in synovial tissues of OA patients and pre-clinical surgically induced OA models [ 49 ]. We have also used complementary markers, e.g., IL-6 and iNOS to confirm the pro-inflammatory phenotype of macrophage populations of interest.…”

Fetal Immunomodulatory Environment Following Cartilage Injury—The Key to CARTILAGE Regeneration?

“…The role of Mɸ in the context of OA pathogenesis is more diverse and dependent on their polarization state that dynamically responds to microenvironmental cues [ 30 , 59 , 60 ]. On the one hand, dysregulation of Mɸ activation with non-resolving persistent macrophage-mediated synovial inflammation is considered as one of the main drivers of both the establishment and progression of OA [ 30 , 31 , 61 ].…”

“…Indeed, the accumulation of M1 polarized macrophages in the intimal lining is the principal morphological characteristic of synovitis and correlates with the progression of OA, stiffness, function and quality of life [ 22 , 29 , 62 , 63 , 64 ]. On the other hand, macrophages are critical immunomodulators in joint injury and have a pivotal role in reinstating articular homeostasis and functional healing [ 30 , 32 , 60 , 62 , 65 , 66 , 67 ]. Corresponding to their diverse functional spectrum, macrophage depletion studies yielded equivocal effects depending on the targeted subpopulations, exacerbating rather than diminishing disease [ 30 , 32 , 62 , 68 , 69 ].…”

Fire Needling Acupuncture Suppresses Cartilage Damage by Mediating Macrophage Polarization in Mice with Knee Osteoarthritis

“… 10 , 11 Macrophages have plastic phenotypes and would adjust to the local microenvironment under physiological and pathological conditions. 12 The activated macrophages exhibit conventionally activated M1 and alternately engaged M2 macrophages under different microenvironments. 13 M1 macrophages represent a pro-inflammatory phenotype, secreting pro-inflammatory cytokines and chemokines such as interleukins-(IL-) 1α, IL-6, and tumor necrosis factor-α (TNF-α); M2 macrophages represent an anti-inflammatory phenotype, releasing anti-inflammatory cytokines such as IL-4, IL-10 and transforming growth factor-β (TGF-β).…”