State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China School & Hospital of Stomatology, Sichuan University, Chengdu, China.
J Periodontal Res. 2022 Oct;57(5):1003-1013. doi: 10.1111/jre.13039. Epub 2022 Aug 5.
The molecular mechanisms mediating external root resorption are poorly understood. Interleukin-33 (IL-33) expression increased remarkably in the periodontal ligament (PDL) under orthodontic loading. The IL-33-driven responses are delicately cell type- and tissue context-dependent. It is unknown how IL-33 act on osteoclastogenesis in the context of root surface. This study aimed to investigate the effect of IL-33 on osteoclastogenesis in the PDL under mechanical loading.
C57BL/6J mice were treated with injections of phosphate buffer saline (PBS) or recombinant mouse IL-33 (rmIL-33, 6 μl, 30 μg/ml), and subjected to models of orthodontic tooth movement. Tartrated resistant acid phosphates (TRAP)-positive cells and IL-33 expressions were examined in the PDL. IL-33 release from human PDL cells (hPDLCs) was detected by ELISA. Cementoblast-like (OCCM-30) cells were cultured in the presence of rmIL-33 to examine the release of osteoclast-regulatory proteins. The effects of rmIL-33 on osteoclastogenesis were examined in vitro in cultures of bone marrow macrophages (BMMs) and in BMMs-OCCM-30 cocultures. Expressions of osteoclast-specific or -related genes and proteins were investigated in BMMs-OCCM-30 cocultures treated with or without rmIL-33, in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody.
Interleukin-33 expressions were upregulated in the PDL under orthodontic loading. Static compressive force enhanced expression and release of IL-33 from hPDLCs. Administration of rmIL-33 resulted in reduced number of TRAP-positive cells in the PDL, and inhibited osteoclast differentiation from BMMs in vitro. OCCM-30 cells had varied osteoprotegerin (OPG) / receptor activator for nuclear factor-κB ligand (RANKL) secretion and increased release of GM-CSF under rmIL-33 stimulation. Treatment with rmIL-33 in BMMs-OCCM-30 cocultures resulted in inhibited differentiation and decreased activity of osteoclasts, and these effects were partially reversed by GM-CSF neutralizing antibody.
Interleukin-33 inhibits osteoclastogenesis in the PDL under orthodontic loading. The anti-osteoclastogenic effects were mediated partly by directly affecting osteoclast precursors and partly by cementoblast-mediated release of GM-CSF.
介导外部牙根吸收的分子机制尚不清楚。白细胞介素-33（IL-33）在正畸加载下牙周韧带（PDL）中表达显著增加。IL-33 驱动的反应对细胞类型和组织背景高度依赖。尚不清楚 IL-33 在牙根表面的情况下如何作用于破骨细胞生成。本研究旨在探讨机械加载下 IL-33 对 PDL 中破骨细胞生成的影响。
C57BL/6J 小鼠用磷酸盐缓冲盐水（PBS）或重组小鼠 IL-33（rmIL-33，6μl，30μg/ml）注射治疗，并进行正畸牙齿移动模型。在 PDL 中检测抗酒石酸酸性磷酸酶（TRAP）阳性细胞和 IL-33 表达。通过 ELISA 检测人牙周膜细胞（hPDLCs）中 IL-33 的释放。在 rmIL-33 存在下培养类成骨细胞样（OCCM-30）细胞，以检测破骨细胞调节蛋白的释放。在骨 marrow macrophages（BMMs）和 BMMs-OCCM-30 共培养物中体外研究 rmIL-33 对破骨细胞生成的影响。在有无 rmIL-33 以及有无粒细胞-巨噬细胞集落刺激因子（GM-CSF）中和抗体的情况下，研究 BMMs-OCCM-30 共培养物中破骨细胞特异性或相关基因和蛋白的表达。
正畸加载下 PDL 中 IL-33 表达上调。静态压缩力增强了 hPDLCs 中 IL-33 的表达和释放。rmIL-33 的给药导致 PDL 中 TRAP 阳性细胞数量减少，并抑制了体外 BMMs 中的破骨细胞分化。OCCM-30 细胞在 rmIL-33 刺激下具有不同的骨保护素（OPG）/核因子-κB 受体激活剂配体（RANKL）分泌和 GM-CSF 释放增加。在 BMMs-OCCM-30 共培养物中用 rmIL-33 处理导致破骨细胞分化和活性降低，这些作用部分被 GM-CSF 中和抗体逆转。
IL-33 抑制正畸加载下 PDL 中的破骨细胞生成。抗破骨细胞作用部分通过直接影响破骨细胞前体，部分通过成骨细胞介导的 GM-CSF 释放来介导。
