Hao Xue, Zhao Jing, Jia Liyuan, Ding Guangyu, Liang Xiaoju, Su Fei, Yang Shuai, Yang Yating, Fan Jing, Zhang Weiping J, Yang Liu, Jie Qiang
Pediatric Hospital, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
Xi'an Key Laboratory of Skeletal Developmental Deformity and Injury Repair, Xi'an, 710054, China.
Bone Res. 2025 Mar 12;13(1):33. doi: 10.1038/s41413-025-00414-3.
Osteoarthritis (OA) is one of the most common degenerative joint diseases in the elderly, increasing in prevalence and posing a substantial socioeconomic challenge, while no disease-modifying treatments available. Better understanding of the early molecular events will benefit the early-stage diagnosis and clinical therapy. Here, we observed the nucleus accumulation of ZBTB20, a member of ZBTB-protein family, in the chondrocytes of early-stage OA. Chondrocytes-specific depletion of Zbtb20 in adult mice attenuated DMM-induced OA progress, restored the balance of extracellular matrix anabolism and catabolism. The NF-κB signaling mediated disturbance of ECM maintenance by ZBTB20 requires its suppression of Pten and consequent PI3K-Akt signaling activation. Furthermore, the subcellular localization of ZBTB20 was modulated by the kinase LATS1. Independent approaches to modulating ZBTB20 via utilizing TRULI and DAPA can restore ECM homeostasis, improving the abnormal behavior and moderating cartilage degeneration. The compounds TRULI and DAPA modulating ZBTB20 may serve as anti-OA drugs.
骨关节炎（OA）是老年人中最常见的退行性关节疾病之一，其患病率不断上升，带来了巨大的社会经济挑战，而目前尚无改善病情的治疗方法。更好地了解早期分子事件将有助于早期诊断和临床治疗。在此，我们观察到ZBTB蛋白家族成员ZBTB20在早期OA软骨细胞中的核积累。成年小鼠软骨细胞特异性缺失Zbtb20可减轻DMM诱导的OA进展，恢复细胞外基质合成代谢和分解代谢的平衡。ZBTB20介导的NF-κB信号通路对ECM维持的干扰需要其对Pten的抑制以及随后PI3K-Akt信号通路的激活。此外，激酶LATS1调节ZBTB20的亚细胞定位。通过使用TRULI和DAPA独立调节ZBTB20的方法可以恢复ECM稳态，改善异常行为并减轻软骨退变。调节ZBTB20的化合物TRULI和DAPA可能用作抗OA药物。
