Excess growth hormone triggers inflammation-associated arthropathy, subchondral bone loss, and arthralgia.
Excess growth hormone triggers inflammation-associated arthropathy, subchondral bone loss, and arthralgia.
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DOI：
10.1016/j.ajpath.2023.02.010
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
S. Poudel;R. Ruff;G. Yildirim;M. Dixit;B. Michot;J. Gibbs;Silvana Durán Ortiz;J. Kopchick;T. Kirsch;S. Yakar
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文献类型：
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作者：
S. Poudel;R. Ruff;G. Yildirim;M. Dixit;B. Michot;J. Gibbs;Silvana Durán Ortiz;J. Kopchick;T. Kirsch;S. Yakar
生长激素（GH）是骨骼生长的关键介质。在人类中，由于垂体腺瘤导致GH分泌过多，见于肢端肥大症患者，导致严重的关节病。本研究探讨了长期过量生长激素对膝关节组织的影响。使用1岁的野生型（WT）和牛GH（bGH）转基因小鼠作为过量GH的模型。与WT小鼠相比，bGH小鼠对机械和热刺激的敏感性增加。对股骨远端软骨下骨的微型计算机断层扫描分析显示，与WT小鼠相比，雄性和雌性bGH的胫骨软骨下骨板的骨小梁厚度显着减少，骨矿物质密度显着降低，与破骨细胞活性增加相关。bGH小鼠表现出关节软骨基质严重丢失、骨赘、滑膜炎和异位软骨形成。bGH小鼠的关节软骨损失与炎症和软骨细胞肥大标志物升高相关。最后，滑膜细胞增生与Ki-67表达增加和bGH小鼠滑膜中p53水平降低相关。与原发性骨关节炎中观察到的低度炎症不同，由过量GH引起的关节病影响所有关节组织并引发严重的炎症反应。这项研究的数据表明，肢端肥大症关节病的治疗应包括抑制异位软骨形成和软骨细胞肥大。
Growth hormone (GH) is a key mediator of skeletal growth. In humans, excess GH secretion due to pituitary adenoma, seen in patients with acromegaly, results in severe arthropathies. This study investigated the effects of long-term excess GH on the knee joint tissues. One year–old wild-type (WT) and bovine GH (bGH) transgenic mice were used as a model for excess GH. bGH mice showed increased sensitivity to mechanical and thermal stimuli, compared with WT mice. Micro–computed tomography analyses of the distal femur subchondral bone revealed significant reductions in trabecular thickness and significantly reduced bone mineral density of the tibial subchondral bone–plate associated with increased osteoclast activity in both male and female bGH compared with WT mice. bGH mice showed severe loss of matrix from the articular cartilage, osteophytosis, synovitis, and ectopic chondrogenesis. Articular cartilage loss in the bGH mice was associated with elevated markers of inflammation and chondrocyte hypertrophy. Finally, hyperplasia of synovial cells was associated with increased expression of Ki-67 and diminished p53 levels in the synovium of bGH mice. Unlike the low-grade inflammation seen in primary osteoarthritis, arthropathy caused by excess GH affects all joint tissues and triggers severe inflammatory response. Data from this study suggest that treatment of acromegalic arthropathy should involve inhibition of ectopic chondrogenesis and chondrocyte hypertrophy.