Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, 410008 Changsha, China.
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, 410008 Changsha, China.
Biomed Res Int. 2020 Nov 9;2020:8861347. doi: 10.1155/2020/8861347. eCollection 2020.
The subchondral bone parallels with the progression of osteoarthritis (OA). However, the biomechanical properties and histopathological changes of subchondral bone changes in the lumbar facet joint (LFJ) after long-term axial loading on the spine have not been explored. In this study, we aimed to investigate the subchondral bone histopathological changes that occur in the LFJ and pain behaviors in a novel bipedal standing mouse model.
Sixteen 8-week-old male C57BL/6 mice were randomly assigned into bipedal standing and control groups. A finite element stimulate model based on the micro-CT data was generated to simulate the von Mises stress distribution on the LFJ during different positions. The spine pain behaviors tests were analysis. In addition, the change in the subchondral bone of the LFJ was assessed by histological and immunohistochemistry staining.
The computerized simulation of the von Mises stress distribution in the superior articular process of LFJ at the spine level 5 in the lying position increased and reached a maximum value at the bipedal standing posture. The spine pain behavior test revealed that the threshold of pressure tolerance decreased significantly in bipedal groups relative to control groups, whereas the mechanical hyperalgesia of the hind paw increased significantly in bipedal groups relative to control groups. The axial load accelerates LFJ degeneration with increased histological scores in bipedal groups. The expression of type II collagen and aggrecan (ACAN) was significantly decreased in the bipedal groups compared with the control groups, whereas the expression of MMP13 was increased. Compared with the control groups, the osteoclast activity was activated with higher TRAP-positive staining and associated with increased CD-31-positive vessels and GCRP-positive nerve ending expression in the subchondral bone of LFJ.
Collectively, long-term axial loading induces the development of spine hyperalgesia in mice associate with increased osteoclast activity and aberrant angiogenesis and nerve invasion into the subchondral bone of LFJ that stimulates the natural pathological change in human LFJ OA. These results indicate that aberrant bone remodeling associate with aberrant nerve innervation in the subchondral bone has a potential as a therapeutic target in LFJ OA pain.
软骨下骨与骨关节炎（OA）的进展平行。然而，在脊柱长期轴向加载后，腰椎小关节（LFJ）的软骨下骨的生物力学特性和组织病理学变化尚未得到探索。在这项研究中，我们旨在研究新型双足站立小鼠模型中 LFJ 软骨下骨组织病理学变化和疼痛行为。
将 16 只 8 周龄雄性 C57BL/6 小鼠随机分为双足站立组和对照组。基于 micro-CT 数据生成有限元刺激模型，以模拟 LFJ 在不同位置的 von Mises 应力分布。分析脊柱疼痛行为测试。此外，通过组织学和免疫组织化学染色评估 LFJ 软骨下骨的变化。
脊柱水平 5 位 LFJ 上关节突 von Mises 应力分布的计算机模拟显示，在双足站立姿势时增加，并达到最大值。脊柱疼痛行为测试显示，双足站立组的压力耐受阈值明显低于对照组，而双足站立组的后爪机械性痛觉过敏明显高于对照组。轴向负荷加速了 LFJ 的退变，双足站立组的组织学评分增加。与对照组相比，双足站立组的 II 型胶原和聚集蛋白（ACAN）表达明显降低，而 MMP13 表达增加。与对照组相比，双足站立组的破骨细胞活性增加，TRAP 阳性染色增加，与软骨下骨中 CD-31 阳性血管和 GCRP 阳性神经末梢表达增加相关。
综上所述，长期轴向负荷导致小鼠脊柱痛觉过敏的发展，与破骨细胞活性增加、异常血管生成和神经侵入软骨下骨有关，这刺激了人类 LFJ OA 的自然病理变化。这些结果表明，软骨下骨异常骨重塑与异常神经支配有关，可能成为 LFJ OA 疼痛的治疗靶点。
