Small heterodimer partner-interacting leucine zipper protein suppresses pain and cartilage destruction in an osteoarthritis model by modulating the AMPK/STAT3 signaling pathway.

Journal article


Moon, Jeonghyeon, Cho, Keun-Hyung, Jhun, JooYeon, Choi, JeongWon, Na, Hyun-Sik, Lee, Jeong Su, Lee, Seung Yoon, Min, Jun-Ki, Shetty, Anan, Park, Sung-Hwan, Kim, Seok Jung and Cho, Mi-La 2024. Small heterodimer partner-interacting leucine zipper protein suppresses pain and cartilage destruction in an osteoarthritis model by modulating the AMPK/STAT3 signaling pathway. Arthritis research & therapy. 26 (1), p. 199.
AuthorsMoon, Jeonghyeon, Cho, Keun-Hyung, Jhun, JooYeon, Choi, JeongWon, Na, Hyun-Sik, Lee, Jeong Su, Lee, Seung Yoon, Min, Jun-Ki, Shetty, Anan, Park, Sung-Hwan, Kim, Seok Jung and Cho, Mi-La
AbstractOsteoarthritis (OA) is a degenerative joint disease caused by the breakdown of joint cartilage and adjacent bone. Joint injury, being overweight, differences in leg length, high levels of joint stress, abnormal joint or limb development, and inherited factors have been implicated in the etiology of OA. In addition to physical damage to the joint, a role for inflammatory processes has been identified as well. Small heterodimer partner-interacting leucine zipper protein (SMILE) regulates transcription and many cellular functions. Among the proteins activated by SMILE is the peroxisome proliferator-activated receptor (PPAR) γ, which mediates the activities of CD4 + T helper cells, including Th1, Th2, and Th17, as well as Treg cells. PPAR-γ binds to STAT3 to inhibit its transcription, thereby suppressing the expression of the NF-κB pathway, and in turn, the expression of the inflammatory cytokines interferon (IFN), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which are sub-signals of STAT3 and NF-κB. OA was induced in control C57BL/6 mice and in C57BL/6-derived SMILE-overexpressing transgenic (SMILE Tg) mice. The protein expression levels in the joint and spleen tissues were analyzed by immunohistochemistry and immunofluorescence images. In addition, flow cytometry was performed for detecting changes of the changes of immune cells. Less cartilage damage and significantly reduced levels of OA biomarkers (MMP13, TIMP3 and MCP-1) were observed in SMILE Tg mice. Immunohistochemistry performed to identify the signaling pathway involved in the link between SMILE expression and OA revealed decreased levels of IL-1β, IL-6, TNF-α, and phosphorylated AMPK in synovial tissues as well as a significant decrease in phosphorylated STAT3 in both cartilage and synovium. Changes in systemic immune cells were investigated via flow cytometry to analyze splenocytes isolated from control and SMILE Tg mice. SMILE Tg mice had elevated proportions of CD4 + IL-4 + cells (Th2) and CD4 + CD25 + Foxp3 + cells (Treg) and a notable decrease in CD4 + IL-17 + cells (Th17). Our results show that overexpressed SMILE attenuates the symptoms of OA, by increasing AMPK signaling and decreasing STAT3, thus reducing the levels of inflammatory immune cells. [Abstract copyright: © 2024. The Author(s).]
KeywordsOsteoarthritis ; Signal transducer and activator of transcription 3 (STAT3); Small heterodimer partner-interacting leucine zipper protein (SMILE); Helper T cell (th cell); Cyclic AMP-response element binding protein Zhangfei (CREBZF)
Year2024
JournalArthritis research & therapy
Journal citation26 (1), p. 199
PublisherBMC
ISSN1478-6362
Official URLhttps://arthritis-research.biomedcentral.com/articles/10.1186/s13075-024-03417-3
FunderKorea Drug Development Fund
Korea Health Industry Development Institute
Publication dates
Online12 Nov 2024
Publication process dates
Accepted16 Oct 2024
Deposited27 Nov 2024
Publisher's version
License
Output statusPublished
Additional information

Publications router.

Permalink -

https://repository.canterbury.ac.uk/item/99v6x/small-heterodimer-partner-interacting-leucine-zipper-protein-suppresses-pain-and-cartilage-destruction-in-an-osteoarthritis-model-by-modulating-the-ampk-stat3-signaling-pathway

Download files


Publisher's version
s13075-024-03417-3.pdf
License: CC BY 4.0

  • 8
    total views
  • 0
    total downloads
  • 5
    views this month
  • 0
    downloads this month

Export as

Related outputs

Oxidized LDL accelerates cartilage destruction and inflammatory chondrocyte death in osteoarthritis by disrupting the TFEB-regulated autophagy-lysosome pathway
Lee, J., Kim, Y., Jhun, J., Na, H., Um, In Gyu, Choi, J., Woo, J., Kim, S., Shetty, A., Kim, S. and Cho, M. 2024. Oxidized LDL accelerates cartilage destruction and inflammatory chondrocyte death in osteoarthritis by disrupting the TFEB-regulated autophagy-lysosome pathway. Immune Network. 24 (3). https://doi.org/10.4110/in.2024.24.e15
Autologous collagen-induced chondrogenesis: From bench to clinical development
Chun, You Seung, Kim, Seon Ae, Kim, Yun Hwan, Lee, Joong Hoon, Shetty, Asode Ananthram and Kim, S. 2023. Autologous collagen-induced chondrogenesis: From bench to clinical development. Medicina (Kaunas, Lithuania). 59 (3), p. 530. https://doi.org/10.3390/medicina59030530
Cartilage regeneration using human umbilical cord blood derived mesenchymal stem cells: A systematic review and meta-analysis
Lee, D., Kim, Seon Ae, Song, Jun-Seob, Shetty, Asode Ananthram, Kim, Bo-Hyoung and Kim, S. 2022. Cartilage regeneration using human umbilical cord blood derived mesenchymal stem cells: A systematic review and meta-analysis. Medicina (Kaunas, Lithuania). 58 (12), p. 1801. https://doi.org/10.3390/medicina58121801
A combination of surgical and chemical induction in a rabbit model for osteoarthritis of the knee
Go, Eun Jeong, Kim, Seon Ae, Cho, Mi-La, Lee, Kwan Soo, Shetty, Asode Ananthram and Kim, S. 2022. A combination of surgical and chemical induction in a rabbit model for osteoarthritis of the knee. Tissue Engineering and Regenerative Medicine. https://doi.org/10.1007/s13770-022-00488-8
Use of injectable acellular dermal matrix combined with negative pressure wound therapy in open diabetic foot amputation
Ahn, Jiyong, Park, Ho Youn, Shetty, Asode Ananthram and Hwang, Wonha 2022. Use of injectable acellular dermal matrix combined with negative pressure wound therapy in open diabetic foot amputation. Journal of Wound Care. 31 (4), pp. 310-320. https://doi.org/10.12968/jowc.2022.31.4.310
Cell therapy for osteonecrosis of femoral head and joint preservation
Chun, You Seung, Lee, Dong Hwan, Won, Tae Gu, Kim, Chan Sik, Shetty, Asode Ananthram and Kim, Seok Jung 2021. Cell therapy for osteonecrosis of femoral head and joint preservation. Journal of Clinical Orthopaedics and Trauma. 24, p. 101713. https://doi.org/10.1016/j.jcot.2021.101713
Biological reconstruction of the joint: Concepts of articular cartilage regeneration and their scientific basis
Vaish, Abhishek, Shanmugasundaram, Saseendar, Kim, Seon Ae, Lee, Dong-Hwan, Shetty, Asode Ananthram and Kim, Seok Jung 2021. Biological reconstruction of the joint: Concepts of articular cartilage regeneration and their scientific basis. Journal of Clinical Orthopaedics and Trauma. 24, p. 101718. https://doi.org/10.1016/j.jcot.2021.101718
Characterization of wild-type and STAT3 signaling-suppressed mesenchymal stem cells obtained from hemovac blood concentrates.
Lee, Dong Hwan, Kim, Seon Ae, Go, Eun Jeong, Yoon, Chi Young, Cho, Mi-La, Shetty, Asode Ananthram and Kim, Seok Jung 2021. Characterization of wild-type and STAT3 signaling-suppressed mesenchymal stem cells obtained from hemovac blood concentrates. Annals of Translational Medicine. 9 (16), p. 1284. https://doi.org/10.21037/atm-21-791
Improved healing of rabbit patellar tendon defects after an atelocollagen injection
Kim, Duck Kyu, Ahn, Jiyong, Kim, Seon Ae, Go, Eun Jeong, Lee, Dong Hwan, Park, Seung Chan, Shetty, Asode Ananthram and Kim, Seok Jung 2021. Improved healing of rabbit patellar tendon defects after an atelocollagen injection. The American Journal of Sports Medicine. 49 (11), pp. 2924-2932. https://doi.org/10.1177/03635465211030508
Comparative characterization of mesenchymal progenitor cells from osteoarthritic and rheumatoid arthritic human articular cartilage
Bm, A., Rao, S., Shetty, S., Shetty, A., Shetty, S., Kim, S. and Mohana Kumar, B. 2021. Comparative characterization of mesenchymal progenitor cells from osteoarthritic and rheumatoid arthritic human articular cartilage. Cytotherapy. 23 (5), p. S56. https://doi.org/10.1016/S1465324921003467
Preliminary results of high fibular osteotomy (HFO) and cartilage regeneration procedure for medial compartment osteoarthritis of knee with varus deformity
Jaheer, H., Shetty, A., Choi, N., Kim, K., Thirumal, S., Song, J., Kim, K., Chun, Y. and Kim, S. 2019. Preliminary results of high fibular osteotomy (HFO) and cartilage regeneration procedure for medial compartment osteoarthritis of knee with varus deformity. Regenerative Therapy. 10, pp. 112-117. https://doi.org/10.1016/j.reth.2019.02.001
A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology.
Shetty, A., Kim, S., Ahmed, S., Trattnig, S., Kim, S. and Jang, H. 2018. A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology. The Annals of the Royal College of Surgeons of England. 100 (3), pp. 240-246. https://doi.org/10.1308/rcsann.2017.0223
Enhancement of healing of long tubular bone defects in rabbits using a mixture of atelocollagen gel and bone marrows aspirate concentrate
Park, H., Shetty, A., Kim, J., Kim, Y., Jang, J., Choi, N., Lee, J. and Kim, S. 2017. Enhancement of healing of long tubular bone defects in rabbits using a mixture of atelocollagen gel and bone marrows aspirate concentrate. Cells Tissues Organs. 203 (6), pp. 339-352. https://doi.org/10.1159/000455829
Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC)
Huh, S., Shetty, A., Ahmed, S., Lee, D. and Kim, S. 2016. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC). Journal of Clinical Orthopaedics and Trauma. 7 (3), pp. 153-156. https://doi.org/10.1016/j.jcot.2016.05.004
Autologous collagen induced chondrogenesis (ACIC: Shetty-Kim technique) - A matrix based acellular single stage arthroscopic cartilage repair technique
Shetty, A., Kim, S., Shetty, V., Jang, J., Huh, S. and Lee, D. 2016. Autologous collagen induced chondrogenesis (ACIC: Shetty-Kim technique) - A matrix based acellular single stage arthroscopic cartilage repair technique. Journal of Clinical Orthopaedics and Trauma. 7 (3), pp. 164-169. https://doi.org/10.1016/j.jcot.2016.05.003