Aspirin reverses inflammatory suppression of chondrogenesis by stabilizing YAP. Issue 4 (10th December 2022)

• Record Type: Journal Article
• Authors: Wang, Xudong; Liao, Hongyi; Liu, Yong; Kang, Yunze; Tu, Qingqiang; Li, Zhiwen; Kang, Yan; Sheng, Puyi; Zhang, Ziji
• Is Part Of: Cell proliferation. Volume 56:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-10
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.13380
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Bone marrow mesenchymal stem cells (BMMSCs) transplantation methods are promising candidates for osteoarthritis (OA) treatment. However, inflammatory factors (such as TNF‐α) that occur at cell transplantation sites are critical factors that impair the effectiveness of the treatment. Previous studies have shown that aspirin (AS) had a regulatory role in stem cell differentiation. However, little is known about the role of AS on the chondrogenesis of BMMSCs. The purpose of this study is to explore the protective role of AS against the negative effects of TNF‐α on BMMSC chondrogenesis. In this study, we investigated the effects of AS and TNF‐α on BMMSCs chondrogenesis by performing the Alcian Blue staining, safranin O‐fast green staining, haematoxylin and eosin staining, and immunohistochemical staining, as well as real‐time RT‐PCR and western blot assays. Our results demonstrated that TNF‐α inhibited chondrogenic differentiation of BMMSCs by disrupting the balance of cartilage metabolism and promoting oxidative stress in BMMSCs, while AS treatment attenuated these effects. Furthermore, a detailed molecular mechanistic analysis indicated that Yes‐associated protein (YAP) played a critical regulatory role in this process. In addition, AS treatment mitigated the progression of cartilage degeneration in a mouse destabilization of the medial meniscus (DMM) model. AS alleviated the inhibitory effect of TNF‐α on chondrogenesis of BMMSCs by stabilizing YAP, which may provide new therapeutic strategies for OA treatment. Abstract : Aspirin mitigates the progression of cartilage degeneration in a mouse DMM model. (A) A schematic of the in vivo experiment. After DMM surgery, mice were injected with aspirin or PBS for 12 weeks ( n = 10 per group). (B) The body weights of mice from different treatment groups were measured after 12 weeks. (C) Representative H&E and safranin O‐fast green staining images of the left knee joint of mice after exposure to different treatments for 8 weeks ( n = 5 per group). (D) The severity of the OA‐like phenotype 8 weeks after DMM surgery in (C) was analysed by the Osteoarthritis Research Society International (OARSI) score system. (E) Representative H&E and safranin O‐fast green staining images of the left knee joint of mice after exposure to different treatments for 12 weeks ( n = 5 per group). (F) The severity of the OA‐like phenotype 12 weeks after DMM surgery in (E) was analysed by the Osteoarthritis Research Society International (OARSI) score system. (G) IHC staining of chondrogenic markers (COL2A1 and SOX9) and catabolic markers (MMP9 and MMP13) in the left knee joint of mice after different treatments for 8 weeks. (H) IHC staining scores of (G). (I) IHC staining of chondrogenic markers (COL2A1 and SOX9) and catabolic markers (MMP9 and MMP13) in the left knee joint of mice after different treatments for 12 weeks. (J) IHC staining scores of (I). * p < 0.05, ** p < 0.01, *** p < 0.001. Scale bars: 0.5 mm (50× figures), 250 μm (100× figures), 100 μm (200× figures), 50 μm (400× figures).