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 hematopoietic cells, including bone-resorbing osteoclasts. The pathogenicity of IgG, i.e. 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.
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