Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China; Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, London NW3 2PF, UK.
Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
Life Sci. 2024 Sep 15;353:122913. doi: 10.1016/j.lfs.2024.122913. Epub 2024 Jul 14.
Temporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration.
Mice ablated for Vdr (Vdr) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined.
Vdr mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr chondrocytes.
VD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ.
颞下颌关节（TMJ）的无菌性炎症可导致退行性病理改变。维生素 D（VD）是维持钙稳态的物质，最近的研究表明，VD 和维生素 D 受体（VDR）在炎症反应中很重要。本研究探讨了 VD-VDR 信号轴在 TMJ 病理退行性变中的抗炎作用。
用挽救饮食喂养 Vdr 缺失（Vdr）的小鼠以避免低钙血症。对小鼠进行单侧前牙交叉咬合（UAC）异常机械刺激，诱导颞下颌紊乱。进行组织学染色、免疫组织化学染色和 micro-CT 分析，以评估 TMJ 病理变化。为了确定无菌性炎症过程中的机制，对野生型（WT）和 Vdr 软骨细胞进行了体外实验，施加压缩机械力加载，检测相关炎症标志物。
Vdr 小鼠在高钙挽救饮食下不会发生佝偻病。与 WT 小鼠相比，机械刺激下 Vdr 小鼠的 TMJ 软骨厚度明显减少。UAC 诱导的骨吸收明显，破骨细胞数量明显增加。Vdr 软骨细胞增殖受到抑制，Il1b、Mmp3 和 Mmp13 的基因表达显著增加。然而，WT 软骨细胞在机械应力作用下，Tnfa 基因表达显著增加，而 Vdr 软骨细胞则没有。
VD-VDR 在异常机械刺激下 TMJ 病理变化中至关重要。Vdr 缺失加剧了炎症反应（排除 TNFα），抑制了软骨细胞增殖，促进了 TMJ 骨吸收。
