Bone and Joint Research Unit, Rheumatology Service, IIS Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Osteoarthritis Cartilage. 2012 Dec;20(12):1619-30. doi: 10.1016/j.joca.2012.08.010. Epub 2012 Aug 27.
Synoviopathy contributes to cartilage degradation in osteoarthritis (OA). Intermittent parathyroid hormone (PTH) [1-34] administration inhibits terminal differentiation of human chondrocytes and prevents cartilage damage. We aimed to determine whether PTH [1-34] could modify synovial changes in experimental OA preceded by osteoporosis (OP).
Twenty osteoporosis (OP) rabbits underwent knee surgery to induce OA. They were administered either saline vehicle or PTH for 10 weeks. Ten healthy rabbits were used as controls. Following sacrifice, synovial changes were assessed by Krenn synovitis score, immunohistochemistry for macrophages (RAM-11), B and T lymphocytes, type I collagen, parathyroid hormone 1 receptor (PTH1R), and anti-proliferating cell nuclear antigen (PCNA). Synovial mRNA levels of Col1A1, IL-1β, cyclooxygenase 2 (COX-2), matrix-degrading metalloproteinases (MMP-9, MMP-13), and monocyte chemotactic protein-1 (MCP-1), as well as protein expression of PTH1R were also determined. Cartilage damage was analyzed by Mankin score.
OPOA + vehicle rabbits showed an increase in synovitis score vs controls (P = 0.003), mainly due to synovial hyperplasia and fibrosis, while PTH reduced these changes (P = 0.017). Mankin and Krenn scores were well correlated in all groups (r = 0.629, P = 0.012). Immunostaining for RAM-11 and B lymphocytes was increased (P ≤ 0.05), whereas PTH1R protein levels tended to be higher in OPOA + vehicle animals vs controls. PTH did not modify RAM-11 staining or PTH1R levels; however, it restored PTH1R localization to the vicinity of synovial vessels. PTH also decreased type I collagen, MCP-1, and MMP-13 expression (P < 0.05), as well as PCNA staining compared to vehicle-treated OPOA rabbits.
In our model of OA aggravated by previous OP, synoviopathy correlated well with cartilage damage. Intermittent PTH [1-34] administration ameliorated both hyperplasia and fibrosis.
滑液病变是骨关节炎（OA）软骨退化的原因之一。间歇性甲状旁腺激素（PTH）[1-34]的给药可以抑制人软骨细胞的终末分化，并防止软骨损伤。我们旨在确定 PTH [1-34]是否可以改变骨质疏松症（OP）前实验性 OA 引起的滑膜变化。
20 只骨质疏松（OP）兔行膝关节手术以诱导 OA。它们接受盐水载体或 PTH 治疗 10 周。10 只健康兔作为对照。处死动物后，通过 Krenn 滑膜炎评分、巨噬细胞（RAM-11）、B 和 T 淋巴细胞、I 型胶原、甲状旁腺激素 1 受体（PTH1R）和增殖细胞核抗原（PCNA）的免疫组织化学评估滑膜变化。还测定了滑膜 mRNA 水平的 Col1A1、IL-1β、环氧化酶 2（COX-2）、基质降解金属蛋白酶（MMP-9、MMP-13）和单核细胞趋化蛋白-1（MCP-1），以及 PTH1R 的蛋白表达。通过 Mankin 评分分析软骨损伤。
OPOA+vehicle 兔的滑膜炎评分较对照组增加（P=0.003），主要是由于滑膜增生和纤维化，而 PTH 则降低了这些变化（P=0.017）。在所有组中，Mankin 和 Krenn 评分均呈高度相关性（r=0.629，P=0.012）。RAM-11 和 B 淋巴细胞的免疫染色增加（P≤0.05），而 OPOA+vehicle 动物的 PTH1R 蛋白水平倾向于高于对照组。PTH 并未改变 RAM-11 染色或 PTH1R 水平；然而，它将 PTH1R 定位恢复到滑膜血管附近。与 OPOA 兔相比，PTH 还降低了 I 型胶原、MCP-1 和 MMP-13 的表达（P<0.05），以及 PCNA 染色。
在我们的由先前 OP 加重的 OA 模型中，滑液病变与软骨损伤密切相关。间歇性 PTH [1-34] 给药可改善增生和纤维化。
