Wang Chih-Chien, Lu Jeng-Wei, Wu Ya-Wun, Chu You-Hsiang, Ho Yi-Jung, Liu Feng-Cheng, Peng Yi-Jen
Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
J Cell Mol Med. 2025 Feb;29(3):e70368. doi: 10.1111/jcmm.70368.
Osteoarthritis (OA) is a degenerative joint disease with a complex aetiology, which includes inflammation, cellular growth dysregulation and extracellular matrix (ECM) degradation. This study investigated the therapeutic potential of a small-molecule compound, 2-amino-4-(3,4,5-trimethoxyphenyl)-4H-benzo[h]chromene-3-carbonitrile (CN7:1h) in modulating these critical biochemical pathways in OA. Cellular models and rat models of OA were used to explore the impact of CN7:1h on the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mechanistic target of rapamycin (mTOR) signalling pathways. Parameters such as autophagy, apoptosis and ECM preservation were evaluated. CN7:1h demonstrated a non-cytotoxic profile at a concentration as high as 140 μM as confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. At a concentration of 5 μM, CN7:1h was shown to inhibit the activation of NF-κB and mTOR pathways. CN7:1h was also shown to promote autophagy and reduce apoptosis in cellular models. In rat models, CN7:1h facilitated cartilage repair and demonstrating the therapeutic efficacy of this compound. In conclusion, CN7:1h is a promising bioactive compound for the modulation of key biochemical pathways with therapeutic benefits in degenerative conditions, such as OA. Its high bioavailability and lack of cytotoxicity make CN7:1h an excellent candidate for further research aimed at clinical applications.
骨关节炎（OA）是一种病因复杂的退行性关节疾病，其病因包括炎症、细胞生长失调和细胞外基质（ECM）降解。本研究调查了一种小分子化合物2-氨基-4-(3,4,5-三甲氧基苯基)-4H-苯并[h]色烯-3-腈（CN7:1h）在调节OA中这些关键生化途径方面的治疗潜力。使用OA的细胞模型和大鼠模型来探究CN7:1h对活化B细胞核因子κB轻链增强子（NF-κB）和雷帕霉素靶蛋白（mTOR）信号通路的影响。评估了自噬、凋亡和ECM保存等参数。经3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定证实，CN7:1h在高达140μM的浓度下表现出无细胞毒性的特性。在5μM的浓度下，CN7:1h被证明可抑制NF-κB和mTOR通路的激活。在细胞模型中，CN7:1h还被证明可促进自噬并减少凋亡。在大鼠模型中，CN7:1h促进了软骨修复，证明了该化合物的治疗效果。总之，CN7:1h是一种有前景的生物活性化合物，可调节关键生化途径，对OA等退行性疾病具有治疗益处。其高生物利用度和无细胞毒性使CN7:1h成为旨在临床应用的进一步研究的优秀候选物。
