Macrophage Phenotypes in Degenerative Joint Diseases

Macrophages are plastic cells and depending on their phenotype can contribute to the inflammatory state of tissues. The main objective of this thesis is to explore the involvement of macrophages, in particular the role of their phenotypes, during processes of joint degeneration. The answers of the following questions contribute to the main objective: • How are macrophages of different phenotypes involved in inflammatory tissue degeneration and degenerative joint disease? • How can modulation of macrophage phenotypes be applied to control either inflammation or their response to biomaterials? The work described in this thesis revealed that pro-inflammatory, anti-inflammatory, and tissue repair macrophages each have their own behavior and association with OA development and progression. The studies in this thesis present methods on specifically modulating a macrophage phenotype within tissue with the ultimate goal: suppressing OA progression. These methods can be interpreted as guidelines for selecting the most suitable approach for modulation while taking into account the stage of the disease, the inflammatory state of the tissue, or the type of biomaterial in case of biomaterial based joint tissue regeneration. The knowledge can be applied to use macrophage phenotype modulation as a t

Cartilage inflammation and degeneration is enhanced by pro-inflammatory (M1) macrophages in vitro, but not inhibited directly by anti-inflammatory (M2) macrophages

Objective Macrophages play a crucial role in the progression of osteoarthritis (OA). Their phenotype may range from pro-inflammatory to anti-inflammatory. The aim of this study was to evaluate the direct effects of macrophage subtypes on cartilage by culturing macrophage conditioned medium (MCM) on human articular cartilage. Design Human OA cartilage explants were cultured with MCM of pro-inflammatory M(IFNγ+TNFα), or anti-inflammatory M(IL-4) or M(IL-10) human monocyte-derived macrophages. To assess effects of anti-inflammatory macrophages, the cartilage was cultured with a combination of MCM phenotypes as well as pre-stimulated with IFNγ+TNFα cartilage before culture with MCM. The reactions of the explants were assessed by gene expression, nitric oxide (NO) production and release of glycosaminoglycans (GAGs). Results M(IFNγ+TNFα) MCM affected OA cartilage by upregulation of IL1B (Interleukin 1β), IL6, MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5), while inhib

Guiding synovial inflammation by macrophage phenotype modulation: An in vitro study towards a therapy for osteoarthritis

Objective: The aims of this study were to modulate inflammation in synovial explants with the compounds: dexamethasone, rapamycin, bone morphogenetic protein 7 (BMP-7) and pravastatin, and to investigate the mod

Monocyte subsets in blood correlate with obesity related response of macrophages to biomaterials in vitro

Macrophages play a key role in the foreign body response. In this study it was investigated whether obesity affects th

Macrophage phenotypes and monocyte subsets after destabilization of the medial meniscus in mice

Macrophages play an important role in the development and progression of osteoarthritis (OA). The aim of this study was to identify macrophage phenotypes in synovium and monocyte subsets in peripheral blood in C57BL/6 mice by destabilizing the medial meniscus (DMM

Preparation and characterization of a decellularized cartilage scaffold for ear cartilage reconstruction

Scaffolds are widely used to reconstruct cartilage. Yet, the fabrication of a scaffold with a highly organized microenvironment that closely resembles native cartilage remains a major challenge. Scaffolds derived from acellular extracellular matrices are able to provide such a microenvironment. Currently, no report specifically on decellularization of full thickness ear cartilage has been published. In this study, decellularized ear cartilage scaffolds were prepared and extensively characterized. Cartilage decellularization was optimized to remove cells and cell remnants from elastic cartilage. Following removal of nuclear material, the obtained scaffolds retained their native collagen and elastin contents as well as their architecture and shape. High magnification scanning electron microscopy showed no obvious difference in matrix density after decellularization. However, glycosaminoglycan content was significantly reduced, resulting in a loss of viscoelastic properties. Additionally, in contact with the scaffolds, human bone-marrow-derived mesenchymal stem cells remained viable and are able to differentiate toward the chondrogenic lineage when cultured in vitro. These results, including the ability to decellularize whole human ears, highlight the clinical potential of decellularization as an improved cartilage reconstruction strategy