Department of Orthodontic, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
J Physiol Pharmacol. 2020 Dec;71(6). doi: 10.26402/jpp.2020.6.06. Epub 2021 Mar 13.
Osteoarthritis (OA) is marked by transcriptional factors. Twist-related protein 1 (TWIST-1) leads to the down-regulation of functional transcriptional regulators such as transforming growth factor-beta 1 (TGF-β1) and Wnt signals, thus blocking the growth and maturation of chondrocytes and providing new pathways to the production of therapeutic targets in OA therapy. Our research assesses the role of aberrant expressions TWIST1 and TGF-β1 as therapeutic targets in the regulation of osteoarthritis by treating with piperlongumine, a known biological agent. Monosodium iodoacetate (MIA) was administered to 32 male Wistar rats into their knee joints to provoke osteoarthritis. A week later, piperlongumine (PL) was orally administered to these rats for a duration of 28 days. The radiographic photos of these rats were documented. The histopathological and serum factors, namely interleukin-1beta (IL-1β), matrix metaloproteinases MMP-1 and MMP-3, were evaluated and their respective results were reported. RNA was extracted and real-time-PCR technique was optimized for TWIST1, TGF-1β and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) determination and sample values were recorded. When treated with PL at 100 mg/kg, our radiographic and histological studies revealed a substantial reduction of OA in rat models but no major improvements were observed at PL 50 mg/kg. Serum levels of IL-1β, MMP-1, and MMP-3 were greatly decreased when treated with PL 100 mg/kg. When administered with a dose higher than PL-100 mg/kg, the relative expressions of TWIST1, mRNA and TGF-β1 mRNA proteins were drastically reduced. Our results suggested that high-dose treatment with piperlongumine was beneficial and effective. TWIST1 and TGF-β1 aberrant expressions contributed as a new transcription factor function and supported the reduction of osteoarthritis intensity with piperlongumine therapy.
骨关节炎（OA）以转录因子为特征。卷曲相关蛋白 1（TWIST-1）导致功能性转录调节剂如转化生长因子-β1（TGF-β1）和 Wnt 信号的下调，从而阻断软骨细胞的生长和成熟，并为 OA 治疗中的治疗靶标的产生提供新途径。我们的研究评估了异常表达 TWIST1 和 TGF-β1 作为治疗靶点在调节骨关节炎中的作用，方法是用胡椒碱（一种已知的生物制剂）进行治疗。将碘乙酸单钠（MIA）注入 32 只雄性 Wistar 大鼠的膝关节中以引发骨关节炎。一周后，这些大鼠口服胡椒碱（PL）治疗 28 天。记录这些大鼠的放射照片。评估了组织病理学和血清因子，即白细胞介素 1β（IL-1β）、基质金属蛋白酶 MMP-1 和 MMP-3，并报告了各自的结果。提取 RNA 并优化实时 PCR 技术以确定 TWIST1、TGF-β1 和甘油醛 3-磷酸脱氢酶（GAPDH），并记录样品值。当用 100mg/kg 的 PL 治疗时，我们的放射学和组织学研究显示大鼠模型中的 OA 显著减少，但在 PL 50mg/kg 时没有观察到明显改善。当用 PL 100mg/kg 治疗时，血清中 IL-1β、MMP-1 和 MMP-3 的水平大大降低。当给予高于 PL-100mg/kg 的剂量时，TWIST1、mRNA 和 TGF-β1 mRNA 蛋白的相对表达量急剧降低。我们的结果表明，高剂量胡椒碱治疗是有益和有效的。TWIST1 和 TGF-β1 的异常表达作为一种新的转录因子功能，支持用胡椒碱治疗减轻骨关节炎的强度。
