Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705; and.
J Immunol. 2019 Jun 15;202(12):3359-3369. doi: 10.4049/jimmunol.1800661. Epub 2019 May 10.
Haptoglobin (Hp), a type of acute-phase protein, is known to have a systemic anti-inflammatory function and to modulate inflammation by directly affecting immune cells, such as T cells, dendritic cells, and macrophages. However, the effects of Hp on osteoclast differentiation are not well studied, even though osteoclast precursor cells belong to a macrophage-monocyte lineage. In this study, we found that the bone volume was reduced, and the number of osteoclasts was increased in Hp-deficient mice compared with wild-type mice. Moreover, our in vitro studies showed that Hp inhibits osteoclastogenesis by reducing the protein level of c-Fos at the early phase of osteoclast differentiation. We revealed that Hp-induced suppression of c-Fos was mediated by increased IFN-β levels. Furthermore, Hp stimulated IFN-β via a TLR4-dependent mechanism. These results demonstrate that Hp plays a protective role against excessive osteoclastogenesis via the Hp-TLR4-IFN-β axis.
触珠蛋白（Hp）是一种急性期蛋白，已知具有全身抗炎功能，并通过直接影响免疫细胞（如 T 细胞、树突状细胞和巨噬细胞）来调节炎症。然而，触珠蛋白对破骨细胞分化的影响尚未得到充分研究，尽管破骨细胞前体细胞属于巨噬细胞-单核细胞谱系。在这项研究中，我们发现与野生型小鼠相比，Hp 缺陷型小鼠的骨量减少，破骨细胞数量增加。此外，我们的体外研究表明，Hp 通过降低破骨细胞分化早期 c-Fos 蛋白水平来抑制破骨细胞生成。我们揭示了 Hp 诱导的 c-Fos 抑制是通过增加 IFN-β 水平介导的。此外，Hp 通过 TLR4 依赖性机制刺激 IFN-β。这些结果表明，Hp 通过 Hp-TLR4-IFN-β 轴发挥保护作用，防止破骨细胞过度生成。
