Cruz Carlos J, Patterson Folly M, Gaire Janak, Gonzalez Julianna, Griffith Jacob L, Philistin Angela, Allen Kyle D
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USA.
Osteoarthr Cartil Open. 2025 Jul 16;7(3):100649. doi: 10.1016/j.ocarto.2025.100649. eCollection 2025 Sep.
Osteoarthritis (OA) often presents with comorbidities such as hypertension, potentially accelerating OA pathogenesis. We hypothesized that hypertension would exacerbate joint-level pathogenesis and OA-related symptoms in a sex-dependent manner.
Male and female Spontaneously Hypertensive rats (hypertensive) and Sprague Dawley rats (normotensive) underwent either medial collateral ligament and medial meniscus transection (OA) or skin incision (sham) in the right knee (N = 80; n = 10/group/sex). Symptoms were measured monthly (gait) and bi-weekly (tactile sensitivity) for 8 weeks. Endpoint histology assessed joint-level damage, neurovascular changes, and cytokine levels in synovial fluid.
At endpoint, hypertensive-OA rats had thinner cartilage across the medial tibial plateau than normotensive-OA rats (non-overlapping 95 % CI), regardless of sex. While not observed in males, hypertensive-OA females developed larger osteophytes (Q1-Q3 = 0.049-0.124 mm) than normotensive-OA females (Q1-Q3 = 0.026-0.047 mm, p = 0.02) and ranked higher for CD31 vasculature in the subchondral bone plate (Q1-Q3 = 18.2-21.5) than normotensive-OA females (Q1-Q3 = 1; p = 0.01). Hypertensive-OA females developed a limping gait, shifting stance times from their OA to non-OA limb (stance time imbalance = 1.20 ± 1.15 %, p = 0.04), offloaded their injured limb quicker (temporal symmetry = 52.5 ± 1.4 %, p < 0.001), and reduced stride lengths (weeks 4 and 8; hypertensive-OA < normotensive-OA, p < 0.001). These gait changes were not observed in normotensive-OA females or males, nor in hypertensive-OA males.
Hypertension worsened OA pathogenesis at the joint level, more substantially affecting joint remodeling and gait compensations in females. Our results encourage further investigation into the pathophysiologic drivers linking hypertension and OA, particularly vascular changes and sex differences.
骨关节炎（OA）常伴有高血压等合并症，可能会加速OA的发病机制。我们假设高血压会以性别依赖的方式加剧关节水平的发病机制和OA相关症状。
雄性和雌性自发性高血压大鼠（高血压组）和Sprague Dawley大鼠（正常血压组）的右膝接受内侧副韧带和内侧半月板横断术（OA组）或皮肤切开术（假手术组）（N = 80；每组/性别n = 10）。在8周内每月（步态）和每两周（触觉敏感性）测量一次症状。终点组织学评估关节水平的损伤、神经血管变化和滑液中的细胞因子水平。
在终点时，无论性别，高血压OA大鼠内侧胫骨平台的软骨都比正常血压OA大鼠薄（95%CI不重叠）。虽然在雄性中未观察到，但高血压OA雌性大鼠比正常血压OA雌性大鼠形成更大的骨赘（四分位间距Q1-Q3 = 0.049-0.124毫米）（Q1-Q3 = 0.026-0.047毫米，p = 0.02），并且在软骨下骨板中的CD31血管分布比正常血压OA雌性大鼠更高（Q1-Q3 = 18.2-21.5）（Q1-Q3 = 1；p = 0.01）。高血压OA雌性大鼠出现跛行步态，将站立时间从OA肢体转移到非OA肢体（站立时间不平衡 = 1.20 ± 1.15%，p = 0.04），更快地卸载受伤肢体（时间对称性 = 52.5 ± 1.4%，p < 0.001），并缩短步长（第4周和第8周；高血压OA < 正常血压OA，p < 0.001）。在正常血压OA雌性或雄性大鼠以及高血压OA雄性大鼠中未观察到这些步态变化。
高血压在关节水平上恶化了OA的发病机制，对雌性大鼠的关节重塑和步态补偿影响更大。我们的结果鼓励进一步研究将高血压和OA联系起来的病理生理驱动因素，特别是血管变化和性别差异。
