Department of Bone Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Immun Inflamm Dis. 2024 Jun;12(6):e1169. doi: 10.1002/iid3.1169.
We aimed to explore the molecular mechanisms through which platelet-rich plasma (PRP) attenuates osteoarthritis (OA)-induced pain, apoptosis, and inflammation.
An in vivo model of OA was established by injuring rats using the anterior cruciate ligament transection method, whereas an in vitro model was generated by exposing chondrocytes to interleukin (IL)-1β. Both models were then treated with PRP.
In both the in vivo and in vitro models, OA led to the suppression of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, whereas treatment with PRP reactivated this molecular axis. Inhibition of the Nrf2/HO-1 pathway using the Nrf2 inhibitor brusatol or through Nrf2 gene silencing counteracted the effects of PRP in reducing the tenderness and thermal pain thresholds of OA rats. Additionally, PRP reduced the mRNA expression of IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and matrix metallopeptidase 13 (MMP-13) and the protein expression of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and caspase-3. Furthermore, inflammation and apoptosis were induced by brusatol treatment or Nrf2 silencing. Additionally, in the in vitro model, PRP treatment increased the proliferation of chondrocytes and attenuated their inflammatory response and apoptosis, effects that were abrogated by Nrf2 depletion.
The Nrf2/HO-1 pathway participates in the PRP-mediated attenuation of OA development by suppressing inflammation and apoptosis.
本研究旨在探讨富血小板血浆（PRP）减轻骨关节炎（OA）诱导的疼痛、细胞凋亡和炎症的分子机制。
采用前交叉韧带切断法建立大鼠 OA 体内模型，用白细胞介素（IL）-1β刺激软骨细胞建立体外模型，并用 PRP 处理这两种模型。
在体内和体外模型中，OA 导致核因子红细胞 2 相关因子 2（Nrf2）/血红素加氧酶-1（HO-1）通路受抑制，而 PRP 处理可重新激活该分子轴。使用 Nrf2 抑制剂布瑞佐特或通过 Nrf2 基因沉默抑制 Nrf2/HO-1 通路，可拮抗 PRP 降低 OA 大鼠触压痛和热痛阈值的作用。此外，PRP 降低了 OA 大鼠的 IL-1β、IL-6、肿瘤坏死因子-α（TNF-α）和基质金属蛋白酶 13（MMP-13）的 mRNA 表达以及 B 细胞淋巴瘤 2（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）的蛋白表达。此外，布瑞佐特处理或 Nrf2 沉默会诱导炎症和细胞凋亡。此外，在体外模型中，PRP 处理可增加软骨细胞的增殖，并减轻其炎症反应和凋亡，而 Nrf2 耗竭则可阻断这些作用。
Nrf2/HO-1 通路通过抑制炎症和细胞凋亡参与 PRP 介导的 OA 发展的抑制作用。
