2. Academic Validation
  3. Blockade of JAK2 retards cartilage degeneration and IL-6-induced pain amplification in osteoarthritis

Blockade of JAK2 retards cartilage degeneration and IL-6-induced pain amplification in osteoarthritis

  • Int Immunopharmacol. 2022 Dec;113(Pt A):109340. doi: 10.1016/j.intimp.2022.109340.
Zhaxi Mima 1,  Ke Wang 2,  Mengmeng Liang 3,  Yu Wang 1,  Chaozhi Liu 1,  Xiaoyu Wei 4,  Fei Luo 4,  Piming Nie 5,  Xuewei Chen 3,  Yuan Xu 6,  Qinyu Ma 7
Affiliations

Affiliations

  • 1 Shigatse Branch, Xinqiao Hospital, Third Military Medical University, Shigatse 857000, China.
  • 2 College of Bioengineering, Chongqing University, 400030 Chongqing, China.
  • 3 Institute of Environment and Operational Medicine, Academy of Military Medicine Sciences, Academy of Military Sciences, Tianjin 300050, China.
  • 4 Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
  • 5 Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
  • 6 Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: 15123161526@163.com.
  • 7 Shigatse Branch, Xinqiao Hospital, Third Military Medical University, Shigatse 857000, China; Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: maqinyu@tmmu.edu.cn.
PMID: 36330910 DOI: 10.1016/j.intimp.2022.109340
Abstract

Osteoarthritis (OA) is a complex chronic inflammatory disease characterized by articular degeneration and pain. Recent studies have identified interleukin 6 (IL-6) as a potential mediator leading to OA, but the therapeutic effects of inhibiting IL-6 signaling in intreating OA need to be further clarified. Here, we identified the intracellular signal transduction induced by recombinant IL-6 and focused on the impact of tyrphostin AG490 (a JAK2 Inhibitor) on cartilage degeneration and OA pain. We found that IL-6 increased the inflammatory cytokines production and hypertrophic markers expression of primary mouse chondrocytes by activating JAK2/STAT3. Meanwhile, tyrphostin AG490 significantly attenuated articular degeneration and osteophyte formation in experimental mice with anterior cruciate ligament transection (ACLT) surgery. In vivo electrophysiological experiments showed that articular stimulation of IL-6 induced spinal hyperexcitability, which was prevented by coinjection of tyrphostin AG490. Specifically, compared with DMSO-treated ACLT mice, tyrphostin AG490 improved ambulate activity of mice and abolished the enhancement of serum bradykinin induced by IL-6. Together, we suggest that tyrphostin AG490 protected against progression of OA and improved OA prognosis by reducing cartilage degeneration and arthritis pain. Our findings provide further evidence for targeting IL-6 signaling in the treatment of OA.

Keywords

Cartilage degeneration; IL-6; Osteoarthritis pain; Tyrphostin AG490.

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