Hu Bin, Du Gongwen
Department of Hand and Foot Surgery, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, Anhui, China.
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, Anhui, China.
Heliyon. 2024 Apr 20;10(9):e30110. doi: 10.1016/j.heliyon.2024.e30110. eCollection 2024 May 15.
Osteoarthritis (OA) is an age-related joint disease characterized by progressive heterogeneous changes in articular cartilage and subchondral bone. Osteoclast stimulating factor 1 (OSTF1) is a small intracellular protein involved in bone formation and bone resorption. However, to our best knowledge, its role in OA is still unclear. In this study, an OA rat model was established by anterior cruciate ligament transection (ALCT). OSTF1 was increased in the cartilage tissues of OA patients and OA rats. Next, the role of OSTF1 in interleukin-1β (IL-1β)-induced chondrocyte apoptosis, inflammation and extracellular matrix degradation was explored through loss of function assays. Strikingly, OSTF1 knockdown relieved IL-1β-induced chondrocyte apoptosis, with decreased cleaved caspase-3 and cleaved PARP levels. Besides, OSTF1 knockdown restrained IL-1β-induced inflammation and degradation of extracellular matrix of chondrocytes. Subsequently, the molecular mechanism of OSTF1 was explored. Transcriptomic analysis revealed the potential gene network map regulated by OSTF1 knockdown. Some differentially expressed genes (DEGs) were involved in regulating the NF-κB signaling pathway. Furthermore, our results demonstrated that OSTF1 knockdown inhibited IL-1β-activated the NF-κB signaling pathway. Ultimately, we analyzed the potential gene network map regulated by OSTF1 and its downstream NF-κB. Bioinformatics analysis showed that 18 DEGs in OSTF1-silenced chondrocytes overlapped with the NF-κB downstream targets. Collectively, our findings indicate that OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway.
骨关节炎（OA）是一种与年龄相关的关节疾病，其特征是关节软骨和软骨下骨出现渐进性异质性变化。破骨细胞刺激因子1（OSTF1）是一种参与骨形成和骨吸收的小细胞内蛋白。然而，据我们所知，其在OA中的作用仍不清楚。在本研究中，通过切断前交叉韧带（ALCT）建立了OA大鼠模型。OA患者和OA大鼠的软骨组织中OSTF1增加。接下来，通过功能丧失实验探讨了OSTF1在白细胞介素-1β（IL-1β）诱导的软骨细胞凋亡、炎症和细胞外基质降解中的作用。令人惊讶的是，敲低OSTF1可减轻IL-1β诱导的软骨细胞凋亡，同时降低裂解的半胱天冬酶-3和裂解的PARP水平。此外，敲低OSTF1可抑制IL-1β诱导的软骨细胞炎症和细胞外基质降解。随后，探讨了OSTF1的分子机制。转录组分析揭示了敲低OSTF1所调控的潜在基因网络图。一些差异表达基因（DEGs）参与调节NF-κB信号通路。此外，我们的结果表明，敲低OSTF1可抑制IL-1β激活NF-κB信号通路。最终，我们分析了由OSTF1及其下游NF-κB调控的潜在基因网络图。生物信息学分析表明，OSTF1沉默的软骨细胞中有18个DEGs与NF-κB下游靶点重叠。总的来说，我们的研究结果表明，敲低OSTF1可通过抑制NF-κB信号通路减轻IL-1β诱导的软骨细胞损伤。
