Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
German Rheumatism Research Centre (DRFZ), a Leibniz Institute, Berlin, Germany.
J Orthop Res. 2024 Dec;42(12):2673-2682. doi: 10.1002/jor.25949. Epub 2024 Aug 3.
Substance P (SP) and a calcitonin-related gene alpha (αCGRP) are implicated in musculoskeletal pain perception and were shown to have different effects on the pathogenesis of osteoarthritis (OA). However, it has not been investigated, whether deficiency for SP or αCGRP impacts pain-related behavior and well-being as well as gait during development of experimental OA. We induced OA in the right knee of wild-type (WT) mice and mice either deficient for SP (tachykinin 1, Tac-1) or αCGRP (male, n = 8 per genotype) by destabilizing the medial meniscus (DMM). We monitored body weight and food and water intake as indicators of wellbeing, determined nest building and composite pain score, and performed CatWalk gait analysis over 12 weeks. Cartilage degeneration was determined by OARSI scoring. The 12-week post-DMM, cartilage degradation in the medial compartment was significantly reduced in Tac1 mice compared to the WT and to αCGRP mice, coinciding with highest unloading of the operated limb in Tac1. Behavioral and gait analysis revealed only minor differences between the genotypes. Paw print area was most prominently reduced in Tac1 over the observation period; at 12 weeks, we found a significant reduction in normalized print area in Tac1 compared to presurgery and to the WT at the same time-point. Calculated weight bearing was significantly reduced only in Tac1. Overall, we observed minor impact of DMM on gait and behavior in the present study. The reduced cartilage damage in the absence of SP might be in part due to reduced loading, however, the mechanism is not clear yet.
P 物质（SP）和降钙素基因相关肽（αCGRP）参与了肌肉骨骼疼痛感知，并且被证明对骨关节炎（OA）的发病机制有不同的影响。然而，目前还没有研究过 SP 或 αCGRP 的缺乏是否会影响实验性 OA 发展过程中的疼痛相关行为、幸福感和步态。我们通过破坏内侧半月板（DMM）在野生型（WT）小鼠和 SP 缺乏型（速激肽 1，Tac-1）或 αCGRP 缺乏型（雄性，每种基因型 n = 8）小鼠的右膝关节中诱导 OA。我们监测体重、食物和水的摄入量作为幸福感的指标，确定筑巢和综合疼痛评分，并在 12 周内进行 CatWalk 步态分析。通过 OARSI 评分确定软骨退化情况。在 DMM 后 12 周，与 WT 和 αCGRP 小鼠相比，Tac1 小鼠内侧隔室的软骨退化明显减少，这与 Tac1 中手术侧的负重明显减少相对应。行为和步态分析显示基因型之间只有微小差异。在整个观察期间，Tac1 的足印面积减少最为明显；在 12 周时，与术前相比，Tac1 的归一化足印面积显著减少，与同一时间点的 WT 相比也显著减少。仅在 Tac1 中计算的承重显著降低。总的来说，在本研究中，DMM 对步态和行为的影响较小。在没有 SP 的情况下，软骨损伤减少可能部分是由于负荷减少，但机制尚不清楚。
