2. Academic Validation
  3. ACY-1215 exhibits anti-inflammatory and chondroprotective effects in human osteoarthritis chondrocytes via inhibition of STAT3 and NF-κB signaling pathways

ACY-1215 exhibits anti-inflammatory and chondroprotective effects in human osteoarthritis chondrocytes via inhibition of STAT3 and NF-κB signaling pathways

  • Biomed Pharmacother. 2019 Jan;109:2464-2471. doi: 10.1016/j.biopha.2018.11.017.
Chao Cheng 1,  Wenshan Shan 2,  Wei Huang 3,  Zhenfei Ding 2,  Guanjun Cui 2,  Fuen Liu 2,  Wei Lu 2,  Jiegou Xu 4,  Wei He 5,  Zongsheng Yin 6
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Fourth Affiliated Hospital of Anhui Medical University, 372#Tun Xi Road, Hefei, 230032, Anhui, China.
  • 2 Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218#Ji Xi Road, Hefei, 230032, Anhui, China.
  • 3 Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218#Ji Xi Road, Hefei, 230032, Anhui, China; Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 17#Lu Jiang Road, Hefei, 230001, Anhui, China.
  • 4 School of Basic Medical Sciences, Anhui Medical University, 81#Mei Shan Road, Hefei, 230032, Anhui, China.
  • 5 School of Basic Medical Sciences, Anhui Medical University, 81#Mei Shan Road, Hefei, 230032, Anhui, China. Electronic address: weihe@ahmu.edu.cn.
  • 6 Department of Orthopaedics, The Fourth Affiliated Hospital of Anhui Medical University, 372#Tun Xi Road, Hefei, 230032, Anhui, China. Electronic address: anhuiyzs@126.com.
PMID: 30551507 DOI: 10.1016/j.biopha.2018.11.017
Abstract

Cartilage degeneration is a basic pathological feature of osteoarthritis (OA), and there is growing evidence that it is associated with inflammation. ACY-1215, a selective HDAC6 Inhibitor, has been reported to have anti-inflammatory effects. Here, we investigated the anti-inflammatory and chondroprotective effects of ACY-1215 in IL-1β-stimulated human primary chondrocytes and C28/I2 cells. The results suggested that ACY-1215 can markedly suppress the expression of inflammatory factors, including IL-1β and IL-6 in human primary chondrocytes and C28/I2 cells. Furthermore, ACY-1215 exerts potent chondroprotection through the amelioration of cartilage degradation by inhibiting the expression of matrix-degrading proteases, including MMP-1 and MMP-13 in chondrocytes. These effects may be related to ACY-1215 induced down-regulation of NF-κB and STAT3 pathways in OA chondrocytes. Taken together, our results show that ACY-1215 may be a potential and promising therapeutic drug for the management of OA.

Keywords

ACY-1215; Chondrocytes; HDAC6; NF-κB; Osteoarthritis; STAT3.

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