Courbon Guillaume, Flammier Sacha, Laroche Norbert, Vico Laurence, Marotte Hubert, Coury Fabienne
SAINBIOSE, INSERM, U1059, LBTO, 42023, Saint-Etienne, France.
University of Lyon, Saint-Etienne, France.
Calcif Tissue Int. 2017 Jun;100(6):575-584. doi: 10.1007/s00223-017-0237-8. Epub 2017 Mar 13.
Syndesmophyte occurrence and axial bone loss were investigated in the heterozygous Tg187 tumor necrosis factor (TNF) transgenic mouse model (Tg-huTNF) of arthritis. Female and male Tg-huTNF mice were compared to wild-type mice (WT) at 2, 4, 6, 8, and 10 weeks. Syndesmophytes, intervertebral disc space, osteoclasts, osteoid surface, and vertebra microarchitecture were assessed by histomorphometry and microcomputed tomography. No spontaneous syndesmophyte formation was detected in Tg-huTNF compared to WT mice. However, increased porosity was observed mainly in peridiscal lumbar vertebra. Accordingly, bone microarchitecture parameters were altered in Tg-huTNF mice, with decrease in bone volume fraction, and trabecular number and thickness after 6 weeks compared to WT (p < 0.05). Osteoclast count and surface were increased (p < 0.01). Moreover, the non-mineralized (osteoid) surface was also increased in Tg-huTNF after 6 weeks (p < 0.01). Despite increased osteoclast and osteoid surfaces, an imbalance between both was observed in favour of osteoid surface at the early phase and then to osteoclast surface. These results demonstrated an axial bone loss in the Tg-huTNF model, additional to the common limb arthritis, related to overexpression of TNF. However, the absence of syndesmophyte and the increase of osteoid surface suggested that chronic inflammation might block bone mineralisation. Finally, the relative increased osteoid surface was not enough to compensate the high osteoclast activity.
在关节炎的杂合Tg187肿瘤坏死因子（TNF）转基因小鼠模型（Tg-huTNF）中研究了韧带骨赘的发生和轴向骨丢失。将雌性和雄性Tg-huTNF小鼠在2、4、6、8和10周时与野生型小鼠（WT）进行比较。通过组织形态计量学和微计算机断层扫描评估韧带骨赘、椎间盘间隙、破骨细胞、类骨质表面和椎骨微结构。与WT小鼠相比，在Tg-huTNF中未检测到自发的韧带骨赘形成。然而，主要在腰椎间盘周围观察到孔隙率增加。因此，Tg-huTNF小鼠的骨微结构参数发生改变，与WT相比，6周后骨体积分数、小梁数量和厚度降低（p<0.05）。破骨细胞计数和表面增加（p<0.01）。此外，6周后Tg-huTNF中的非矿化（类骨质）表面也增加（p<0.01）。尽管破骨细胞和类骨质表面增加，但在早期观察到两者之间存在失衡，有利于类骨质表面，然后是破骨细胞表面。这些结果表明，在Tg-huTNF模型中，除了常见的肢体关节炎外，还存在与TNF过表达相关的轴向骨丢失。然而，韧带骨赘的缺乏和类骨质表面的增加表明慢性炎症可能会阻碍骨矿化。最后，相对增加的类骨质表面不足以补偿高破骨细胞活性。
