Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do not affect arthritis-mediated bone loss.
Immunoglobulin G complexes without sialic acids enhance osteoclastogenesis but do not affect arthritis-mediated bone loss.
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DOI：
10.1111/sji.13009
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发表时间：
2021-05
影响因子：
3.7
通讯作者：
Engdahl C
中科院分区：
文献类型：
--
作者：
Sehic E;Westerlund A;Lagerquist MK;Lerner UH;Carlsten H;Henning P;Engdahl C
免疫球蛋白G （IgG）在清除和识别先前呈递的抗原中很重要，激活后，IgG可以与造血细胞（包括骨吸收破骨细胞）上的Fcγ受体（Fcγ rs）相互作用。IgG的致病性，即通过fc - γ - rs引起刺激作用的能力，可以通过附着糖部分（包括唾液酸）来调节。人igg和自身抗体与自身免疫性疾病的骨质流失有关。然而，多克隆小鼠IgG通过FcγRs对骨丢失的影响尚不清楚。在这里，我们研究了热聚集激活的小鼠多克隆IgG复合物是否对小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质流失。通过小鼠破骨细胞的细胞培养，我们发现不含唾液酸的IgG复合物（去IgG复合物）增强核因子κ Β配体受体激活剂（RANKL）刺激的破骨细胞生成，这一效应与FcγRIII表达增加有关。使用关节炎介导的骨质流失的体内模型，将IgG复合物注射到关节炎膝关节，对关节炎的严重程度或关节炎介导的骨质流失程度没有影响。有趣的是，在无关节炎的膝关节中注射IgG复合物增加了破骨细胞的形成和骨侵蚀。我们的研究结果表明，活化的de - IgG复合物对关节炎介导的骨质流失没有附加作用。然而，IgG复合物可增强小鼠破骨细胞生成并增强非关节炎骨骼的局部骨侵蚀，进一步证实了适应性免疫系统与骨骼之间的联系。
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.
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影响因子：
46.9
作者：
Li, HJ;Sethuraman, N;Gerngross, TU
通讯作者：
Gerngross, TU
影响因子：
2
作者：
Scherer, H. Ulrich;Wang, Jun;Wuhrer, Manfred
通讯作者：
Wuhrer, Manfred
DOI：
10.1073/pnas.1301001110
发表时间：
2013-06-25
影响因子：
11.1
作者：
Seeling, Michaela;Hillenhoff, Ulrike;Nimmerjahn, Falk
通讯作者：
Nimmerjahn, Falk
影响因子：
27.4
作者：
Rombouts, Yoann;Ewing, Ewoud;Scherer, Hans U.
通讯作者：
Scherer, Hans U.
影响因子：
27.4
作者：
Grevers, Lilyanne C.;de Vries, Teun J.;van Lent, Peter L. E. M.
通讯作者：
van Lent, Peter L. E. M.