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Abstract：
OBJECTIVE: Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1-34) is commonly used to treat osteoporosis. However, little is known about its effects on FJD induced by estrogen deficiency. This study aims to investigate the effects of PTH (1-34) on FJD induced by estrogen deficiency and the underlying pathogenesis of the disease.
METHODS: Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1-34) or 17β-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/β-catenin signaling activity in the cartilage and subchondral bone of the L4-L5 FJs and serum biomarkers were analyzed.
RESULTS: Administration of PTH (1-34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1-34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1-34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and β-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1-34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/β-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/β-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status.
CONCLUSIONS: Wnt/β-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1-34) is effective in treating this disease with better efficacy than 17β-estradiol, and the efficacy may be attributed to its restoration of Wnt/β-catenin signaling.
METHODS: Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1-34) or 17β-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/β-catenin signaling activity in the cartilage and subchondral bone of the L4-L5 FJs and serum biomarkers were analyzed.
RESULTS: Administration of PTH (1-34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1-34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1-34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and β-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1-34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/β-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/β-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status.
CONCLUSIONS: Wnt/β-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1-34) is effective in treating this disease with better efficacy than 17β-estradiol, and the efficacy may be attributed to its restoration of Wnt/β-catenin signaling.
摘要：
目的：小关节变性（FJD）是下腰痛的主要原因。甲状旁腺激素(PTH)(1-34)通常用于治疗骨质疏松症。然而,它对雌激素缺乏引起的FJD的影响知之甚少。本研究旨在探讨PTH(1-34)对雌激素缺乏诱导的FJD的影响及其发病机制。
方法：将40只3月龄雌性Sprague-Dawley大鼠随机分为4组：30只接受双侧卵巢切除术（OVX），然后用生理盐水治疗12周，PTH（1-34）或17β-雌二醇（E2），10例接受假手术，然后给予生理盐水。分析L4-L5FJ的软骨和软骨下骨中的状态和Wnt/β-catenin信号传导活性以及血清生物标志物。
结果：给予PTH（1-34）和E2改善了软骨损伤，并显著降低MMP-13和caspase-3水平和软骨细胞凋亡。PTH（1-34）但E2没有显着增加软骨厚度，软骨细胞的数量，和aggrecan的表达式。PTH（1-34）显着改善了软骨下骨的微结构参数，增加胶原蛋白I和骨钙蛋白的表达，RANKL/OPG比值降低。E2处理显著提高了去卵巢大鼠软骨下骨的OPG水平,降低了RANKL/OPG比值,但是它并没有显着改善软骨下骨的微结构参数。OVX大鼠关节软骨和软骨下骨中Wnt3a和β-catenin的表达明显降低，但PTH(1-34)可以增加这些蛋白的表达。E2仅在软骨中显著增加Wnt/β-catenin通路的活性,但不是在软骨下骨.Wnt/β-catenin信号的恢复与FJs状态相关参数的改善有明显的相关性。
结论：Wnt/β-catenin信号传导可能是雌激素缺乏导致FJD的潜在治疗靶点。PTH（1-34）在治疗这种疾病方面有效，疗效优于17β-雌二醇，和功效可能归因于其对Wnt/β-catenin信号传导的恢复。
方法：将40只3月龄雌性Sprague-Dawley大鼠随机分为4组：30只接受双侧卵巢切除术（OVX），然后用生理盐水治疗12周，PTH（1-34）或17β-雌二醇（E2），10例接受假手术，然后给予生理盐水。分析L4-L5FJ的软骨和软骨下骨中的状态和Wnt/β-catenin信号传导活性以及血清生物标志物。
结果：给予PTH（1-34）和E2改善了软骨损伤，并显著降低MMP-13和caspase-3水平和软骨细胞凋亡。PTH（1-34）但E2没有显着增加软骨厚度，软骨细胞的数量，和aggrecan的表达式。PTH（1-34）显着改善了软骨下骨的微结构参数，增加胶原蛋白I和骨钙蛋白的表达，RANKL/OPG比值降低。E2处理显著提高了去卵巢大鼠软骨下骨的OPG水平,降低了RANKL/OPG比值,但是它并没有显着改善软骨下骨的微结构参数。OVX大鼠关节软骨和软骨下骨中Wnt3a和β-catenin的表达明显降低，但PTH(1-34)可以增加这些蛋白的表达。E2仅在软骨中显著增加Wnt/β-catenin通路的活性,但不是在软骨下骨.Wnt/β-catenin信号的恢复与FJs状态相关参数的改善有明显的相关性。
结论：Wnt/β-catenin信号传导可能是雌激素缺乏导致FJD的潜在治疗靶点。PTH（1-34）在治疗这种疾病方面有效，疗效优于17β-雌二醇，和功效可能归因于其对Wnt/β-catenin信号传导的恢复。
