Macrophages in aseptic loosening: Characteristics, functions, and mechanisms

Abstract

Aseptic loosening (AL) is the most common complication of total joint arthroplasty (TJA). Both local inflammatory response and subsequent osteolysis around the prosthesis are the fundamental causes of disease pathology. As the earliest change of cell behavior, polarizations of macrophages play an essential role in the pathogenesis of AL, including regulating inflammatory responses and related pathological bone remodeling. The direction of macrophage polarization is closely dependent on the microenvironment of the periprosthetic tissue. When the classically activated macrophages (M1) are characterized by the augmented ability to produce proinflammatory cytokines, the primary functions of alternatively activated macrophages (M2) are related to inflammatory relief and tissue repair. Yet, both M1 macrophages and M2 macrophages are involved in the occurrence and development of AL, and a comprehensive understanding of polarized behaviors and inducing factors would help in identifying specific therapies. In recent years, studies have witnessed novel discoveries regarding the role of macrophages in AL pathology, the shifts between polarized phenotype during disease progression, as well as local mediators and signaling pathways responsible for regulations in macrophages and subsequent osteoclasts (OCs). In this review, we summarize recent progress on macrophage polarization and related mechanisms during the development of AL and discuss new findings and concepts in the context of existing work.

Erdr1 orchestrates macrophage polarization and determines cell fate via dynamic interplay with YAP1 and Mid1

“…M2 macrophage undergo apoptotic death, which elicit anti-inflammatory response. By contrast, M1 macrophage undergo pyroptosis, which is a proinflammatory form of cell death [50][51][52] . Our data show that both Erdr1-177 and Erdr1-145 protein supplementation promote unstimulated macrophages death (Supplemental Fig.…”

Calycosin alleviates titanium particle‐induced osteolysis by modulating macrophage polarization and subsequent osteogenic differentiation

“…M1 macrophages act as a paracrine inhibitor of osteogenesis, 5 while M2 macrophages augment tissue repair and promote osteogenesis by secreting anti‐inflammatory cytokines 6 . Regulating the polarization balance of macrophages may serve as an effective strategy to alleviate wear particle‐induced osteolysis and promote bone formation 7 …”

“…6 Regulating the polarization balance of macrophages may serve as an effective strategy to alleviate wear particle-induced osteolysis and promote bone formation. 7 Natural products are a main source of new drug development, and natural small molecules derived from traditional Chinese medicines have a wide spectrum of biological activities and exhibit promising prospects in disease prevention and treatment. 8 Astragalus membranaceous (AM) is a common food-origin Chinese medicine with a long history of treating osteoporosis, inflammation and other related diseases.…”

Wogonin induces apoptosis in macrophages by exhibiting cytotoxic and genotoxic effects

“…Macrophages, an essential type of leukocyte in the innate immune system, play an important role in defending the body against invading pathogens, including bacteria, viruses, and fungi. [1][2][3][4] Faced with pathogens, macrophages become activated and release toxic materials that disrupt the pathogens. 1,[5][6][7] However, overproduction of toxic materials can harm healthy peripheral tissues and organs and causes an inflammatory response.…”

“…6,8 Macrophages play a crucial role in tissue repair, regeneration, and remodeling. [1][2][3] Macrophage overactivation can lead to severe illness, such as respiratory diseases, autoimmune rheumatic diseases, atherosclerosis, and diabetes. [9][10][11] Macrophage overaction has cytotoxic and genotoxic effects, leading to apoptosis.…”