Chen Longting, Zhong Yiming, Sun Shang, Yang Zihuan, Hong Haofeng, Zou Da, Song Chunli, Li Weishi, Leng Huijie
Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
Engineering Research Center of Bone and Joint Precision Medicine, Beijing, 100191, China.
Heliyon. 2023 Jun 22;9(6):e17595. doi: 10.1016/j.heliyon.2023.e17595. eCollection 2023 Jun.
Endplate osteochondritis is considered one of the major causes of intervertebral disc degeneration (IVDD) and low back pain. Menopausal women have a higher rate of endplate cartilage degeneration than similarly aged men, but the related mechanisms are still unclear. Subchondral bone changes, mainly mediated by osteoblasts and osteoclasts, are considered an important reason for the degeneration of cartilage. This work explored the role of osteoclasts in endplate cartilage degeneration, as well as its underlying mechanisms. A rat ovariectomy (OVX) model was used to induce estrogen deficiency. Our experiments indicated that OVX significantly promoted osteoclastogenesis and anabolism and catabolism changes in endplate chondrocytes. OVX osteoclasts cause an imbalance between anabolism and catabolism in endplate chondrocytes, as shown by a decrease in anabolic markers such as Aggrecan and Collagen II, and an increase in catabolic markers such as a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and matrix metalloproteinases (MMP13). Osteoclasts were also confirmed in this study to be able to secrete HtrA serine peptidase 1 (HTRA1), which resulted in increased catabolism in endplate chondrocytes through the NF-κB pathway under estrogen deficiency. This study demonstrated the involvement and mechanism of osteoclasts in the anabolism and catabolism changes of endplate cartilage under estrogen deficiency, and proposed a new strategy for the treatment of endplate osteochondritis and IVDD by targeting HTRA1.
终板骨软骨炎被认为是椎间盘退变（IVDD）和腰痛的主要原因之一。绝经后女性终板软骨退变的发生率高于同龄男性，但其相关机制仍不清楚。软骨下骨的变化主要由成骨细胞和破骨细胞介导，被认为是软骨退变的重要原因。这项研究探讨了破骨细胞在终板软骨退变中的作用及其潜在机制。采用大鼠卵巢切除（OVX）模型诱导雌激素缺乏。我们的实验表明，OVX显著促进破骨细胞生成以及终板软骨细胞的合成代谢和分解代谢变化。OVX破骨细胞导致终板软骨细胞合成代谢和分解代谢失衡，表现为聚集蛋白聚糖和胶原蛋白II等合成代谢标志物减少，而具有血小板反应蛋白基序的解聚素和金属蛋白酶5（ADAMTS5）和基质金属蛋白酶（MMP13）等分解代谢标志物增加。本研究还证实破骨细胞能够分泌HtrA丝氨酸蛋白酶1（HTRA1），在雌激素缺乏的情况下，通过NF-κB途径导致终板软骨细胞分解代谢增加。本研究证明了破骨细胞在雌激素缺乏情况下终板软骨合成代谢和分解代谢变化中的作用及机制，并提出了一种通过靶向HTRA1治疗终板骨软骨炎和IVDD的新策略。
