Parathyroid hormone (1-34) ameliorates cartilage degeneration and subchondral bone deterioration in collagenase-induced osteoarthritis model in mice.
Parathyroid hormone (1-34) ameliorates cartilage degeneration and subchondral bone deterioration in collagenase-induced osteoarthritis model in mice.
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DOI：
10.1302/2046-3758.910.bjr-2020-0018.r1
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发表时间：
2020-10
影响因子：
4.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Shao LT;Gou Y;Fang JK;Hu YP;Lian QQ;Zhang YY;Wang YD;Tian FM;Zhang L
甲状旁腺激素(PTH)(1-34)在骨性关节炎(OA)的发展中显示出防止软骨和软骨下骨退变的潜力。我们评估了不同浓度的PTH(1-34)对胶原酶诱导的小鼠骨性关节炎模型骨和软骨代谢的影响，并研究了PTH(1-34)在这一过程中是否影响JAK2/STAT3信号通路。建立胶原酶诱导的C57BL/6小鼠骨性关节炎模型。术后立即给予甲状旁腺素(1-34)(10μg/kg/d或40μg/kg/d)治疗，持续6周。软骨病理通过肉眼、组织学和免疫组织化学评价。TUNEL染色分析细胞凋亡情况。采用微电脑断层扫描(Micro-CT)测量软骨下骨的骨量和微结构。软骨基质分解代谢增强，软骨细胞凋亡率增加，JAK2/STAT3和p-JAK2/p-STAT3在软骨中过表达。PTH(1-34)治疗可预防上述改变，低剂量组和高剂量组之间无显著差异。Micro-CT分析显示，骨密度、骨体积/骨小梁体积比(Bv/Tv)、骨小梁厚度(Tb.Th)在骨性关节炎组明显低于假手术组、甲状旁腺素10μg组和甲状旁腺素40μg组，而甲状旁腺素40μg组显著高于甲状旁腺素10μg组。在胶原酶诱导的小鼠骨性关节炎模型中，间歇给予甲状旁腺素(1-34)对软骨和软骨下骨均显示出剂量依赖性的保护作用，这可能参与了JAK2/STAT3信号通路的调节。引用本文：骨关节资源2020；9(10)：675-688。
Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688.