Department of Rheumatology and Inflammation Research, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Internal Medicine and Clinical Nutrition, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Scand J Immunol. 2021 May;93(5):e13009. doi: 10.1111/sji.13009. Epub 2020 Dec 22.
Immunoglobulin G (IgG) is important in clearance and recognition of previously presented antigens and after activation, IgGs can interact with the Fc gamma receptors (FcγRs) on haematopoietic cells, including bone-resorbing osteoclasts. The pathogenicity of IgG, that is the ability to elicit stimulatory effects via FcγRs, can be modulated by attachment of sugar moieties, including sialic acids. Human IgGs and autoantibodies are associated with bone loss in autoimmune disease. However, the impact of polyclonal murine IgG via FcγRs on bone loss is poorly understood. Here, we investigate if heat-aggregated activated murine polyclonal IgG complexes have any direct effects on murine osteoclasts and if they modulate arthritis-mediated bone loss. Using cell cultures of murine osteoclasts, we show that IgG complexes without sialic acids (de-IgG complexes) enhance receptor activator of nuclear factor kappa-Β ligand (RANKL)-stimulated osteoclastogenesis, an effect associated with increased FcγRIII expression. Using an in vivo model of arthritis-mediated bone loss, where IgG complexes were injected into arthritic knees, no effect on the severity of arthritis or the degree of arthritis-mediated bone loss was detected. Interestingly, injection of de-IgG complexes into non-arthritic knees increased osteoclast formation and enhanced bone erosions. Our findings show that activated de-IgG complexes have no additive effect on arthritis-mediated bone loss. However, de-IgG complexes potentiate murine osteoclastogenesis and enhance local bone erosion in non-arthritic bones, further confirming the link between the adaptive immune system and bone.
免疫球蛋白 G（IgG）在清除和识别以前呈现的抗原中很重要，并且在激活后，IgG 可以与造血细胞上的 Fcγ 受体（FcγRs）相互作用，包括破骨细胞。IgG 的致病性，即通过 FcγRs 引发刺激作用的能力，可以通过糖基的附着来调节，包括唾液酸。人 IgG 和自身抗体与自身免疫性疾病中的骨丢失有关。然而，FcγRs 介导的多克隆鼠 IgG 的致病作用对骨丢失的影响知之甚少。在这里，我们研究了热聚集激活的多克隆鼠 IgG 复合物是否对鼠破骨细胞有任何直接影响，以及它们是否调节关节炎介导的骨丢失。通过鼠破骨细胞的细胞培养，我们表明没有唾液酸的 IgG 复合物（去 IgG 复合物）增强核因子 kappa-B 配体（RANKL）刺激的破骨细胞生成，这种作用与 FcγRIII 表达增加有关。使用关节炎介导的骨丢失的体内模型，将 IgG 复合物注射到关节炎膝关节中，未检测到对关节炎严重程度或关节炎介导的骨丢失程度的影响。有趣的是，将去 IgG 复合物注射到非关节炎膝关节中会增加破骨细胞的形成并增强骨侵蚀。我们的研究结果表明，激活的去 IgG 复合物对关节炎介导的骨丢失没有附加作用。然而，去 IgG 复合物增强了鼠破骨细胞生成，并增强了非关节炎骨骼中的局部骨侵蚀，进一步证实了适应性免疫系统与骨骼之间的联系。
