甲状旁腺激素（1-34）可延缓腰椎小关节退变，并激活去卵巢大鼠的 Wnt/β-连环蛋白信号通路。

Parathyroid hormone (1-34) retards the lumbar facet joint degeneration and activates Wnt/β-catenin signaling pathway in ovariectomized rats.

机构信息

Department of Orthopaedic Surgery, Tianjin Hospital, Tianjin University, Tianjin, China.

Department of Orthopaedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

出版信息

J Orthop Surg Res. 2024 Jun 14;19(1):352. doi: 10.1186/s13018-024-04817-6.

DOI:10.1186/s13018-024-04817-6

PMID:38877549

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11177467/

Abstract

PURPOSE

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.

CONCLUSION

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

小关节退行性变（FJD）是腰痛的主要原因。甲状旁腺激素（PTH）（1-34）常用于治疗骨质疏松症。然而，关于其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）对雌激素缺乏引起的 FJD 的影响及其发病机制。

方法

40 只 3 月龄雌性 Sprague-Dawley 大鼠随机分为四组：30 只接受双侧卵巢切除术（OVX），随后接受生理盐水、PTH（1-34）或 17β-雌二醇（E2）治疗 12 周，10 只接受假手术，随后给予生理盐水。分析 L4-L5 FJ 软骨和软骨下骨的 Wnt/β-catenin 信号活性和血清生物标志物。

结果

PTH（1-34）和 E2 治疗可改善软骨病变，显著降低 MMP-13 和 caspase-3 水平及软骨细胞凋亡。PTH（1-34）而非 E2 可显著增加软骨厚度、软骨细胞数量和聚集蛋白聚糖的表达。PTH（1-34）可显著改善软骨下骨的微观结构参数，增加胶原 I 和骨钙素的表达，降低 RANKL/OPG 比值。E2 治疗可显著增加去卵巢大鼠软骨下骨中 OPG 水平，降低 RANKL/OPG 比值，但对软骨下骨微观结构参数无明显改善。Wnt3a 和β-catenin 在关节软骨和软骨下骨中的表达在 OVX 大鼠中显著降低，但 PTH（1-34）可增加这些蛋白的表达。E2 仅显著增加软骨中 Wnt/β-catenin 通路的活性，而不在软骨下骨中。Wnt/β-catenin 信号的恢复与 FJ 状态相关参数的改善明显相关。