Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Molecular Pharmacology
  4. Volume 17, Issue 1
  5. Article
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
file format pdf download PDF
side by side viewer icon HTML

Abstract

Objective

This study aimed to explore the repair effect of siRNA-mediated double silencing of the mechanically sensitive ion channels Piezo1 and TRPV4 proteins on a rat model of osteoarthritis.

Methods

Piezo1 and TRPV4 interference plasmids were constructed using siRNA technology. Sprague Dawley (SD) rats were divided into four groups: the model group, siRNA-Piezo1, siRNA-TRPV4, and double gene silencing groups. Improved Mankin and OARSI scores were calculated based on H&E staining and Safranin O-fast green staining. Immunohistochemical staining was used to determine expression levels of aggrecan and Collagen II proteins. Piezo1, TRPV4, Aggrecan, and Collagen II mRNA expression in knee joint cartilage tissue were assessed using qRT-PCR.

Results

Lentivirus-mediated siRNA plasmids (siRNA-Piezo1, siRNA-TRPV4, and double-gene siRNA silencing plasmids) achieved > 90% transfection efficiency in chondrocytes. RT-PCR results indicated that double-gene siRNA silencing plasmids silenced Piezo1 and TRPV4 mRNA expression ( < 0.05). Modified Mankin and OARSI scores revealed that the repair effect in the double gene silencing group was significantly better than that of the siRNA-Piezo1 and siRNA-TRPV4 groups ( < 0.05). Relative expression of aggrecan and collagen II mRNA in the double gene-silenced group was significantly higher than in the siRNA-Piezo1 and siRNA-TRPV4 groups ( < 0.05).

Conclusion

Double silencing Piezo1 and TRPV4 plays a key role in cartilage repair in an osteoarthritic rat model by promoting the expression of Aggrecan and Collagen II.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/cmp/10.2174/0118761429317745241017114020
2024-01-01
2025-05-02

  • From This Site

    /content/journals/cmp/10.2174/0118761429317745241017114020
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
The full text of this item is not currently available.

References

  1. YaoQ. WuX. TaoC. GongW. ChenM. QuM. ZhongY. HeT. ChenS. XiaoG. Osteoarthritis: Pathogenic signaling pathways and therapeutic targets.Signal Transduct. Target. Ther.2023815610.1038/s41392‑023‑01330‑w36737426
     [Google Scholar]
  2. AllenK.D. ThomaL.M. GolightlyY.M. Epidemiology of osteoarthritis.Osteoarthritis Cartilage202230218419510.1016/j.joca.2021.04.02034534661
     [Google Scholar]
  3. Barbeau-GrégoireM. OtisC. CournoyerA. MoreauM. LussierB. TroncyE. A 2022 systematic review and meta-analysis of enriched therapeutic diets and nutraceuticals in canine and feline osteoarthritis.Int. J. Mol. Sci.202223181038410.3390/ijms23181038436142319
     [Google Scholar]
  4. HodgkinsonT. KellyD.C. CurtinC.M. O’BrienF.J. Mechanosignalling in cartilage: An emerging target for the treatment of osteoarthritis.Nat. Rev. Rheumatol.2022182678410.1038/s41584‑021‑00724‑w34934171
     [Google Scholar]
  5. DeaboldK. MontalbanoC. MisciosciaE. Feline osteoarthritis management.Vet. Clin. North Am. Small Anim. Pract.202353487989610.1016/j.cvsm.2023.02.01536964025
     [Google Scholar]
  6. HuangWH. DongJP. Patisiran, the first rare disease treatment drug based on RNA therapy.Chin J New Drugs Clin Med20183710560
     [Google Scholar]
  7. WangL. YouX. LotinunS. ZhangL. WuN. ZouW. Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk.Nat. Commun.202011128210.1038/s41467‑019‑14146‑631941964
     [Google Scholar]
  8. AtchaH. JairamanA. HoltJ.R. MeliV.S. NagallaR.R. VeerasubramanianP.K. BrummK.T. LimH.E. OthyS. CahalanM.D. PathakM.M. LiuW.F. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing.Nat. Commun.2021121325610.1038/s41467‑021‑23482‑534059671
     [Google Scholar]
  9. LaiA. CoxC.D. Chandra SekarN. ThurgoodP. JaworowskiA. PeterK. BaratchiS. Mechanosensing by Piezo1 and its implications for physiology and various pathologies.Biol. Rev. Camb. Philos. Soc.202297260461410.1111/brv.1281434781417
     [Google Scholar]
  10. BrylkaL.J. AlimyA.R. Tschaffon-MüllerM.E.A. JiangS. BallhauseT.M. BaranowskyA. von KrogeS. DelsmannJ. PawlusE. EghbalianK. PüschelK. SchoppaA. Haffner-LuntzerM. BeechD.J. BeilF.T. AmlingM. KellerJ. IgnatiusA. YorganT.A. RolvienT. SchinkeT. Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development.Bone Res.20241211210.1038/s41413‑024‑00315‑x38395992
     [Google Scholar]
  11. XingR. WangP. ZhaoL. XuB. ZhangN. LiX. Mechanism of TRPA1 and TRPV4 participating in mechanical hyperalgesia of rat experimental knee osteoarthritis.Arch. Rheumatol.20173229610410.5606/ArchRheumatol.2017.606130375565
     [Google Scholar]
  12. WuS. ZhouH. LingH. SunY. LuoZ. NgoT. FuY. WangW. KongY. LIPUS regulates the progression of knee osteoarthritis in mice through primary cilia-mediated TRPV4 channels.Apoptosis2024295-678579810.1007/s10495‑024‑01950‑938517601
     [Google Scholar]
  13. ZhaoC. SunG. LiY. KongK. LiX. KanT. YangF. WangL. WangX. Forkhead box O3 attenuates osteoarthritis by suppressing ferroptosis through inactivation of NF-κB/MAPK signaling.J. Orthop. Translat.20233914716210.1016/j.jot.2023.02.00537188001
     [Google Scholar]
  14. FujibayashiS. KiyonoT. EndoY. TaniT. TateH. BaiL. SuganoE. TomitaH. FukudaT. Increased lentivirus titer using ultra expression vectors.Anal. Biochem.202366911511910.1016/j.ab.2023.11511936958509
     [Google Scholar]
  15. YangQ.N. CaoY. ZhouY.W. Expression characteristics of piezo1 protein in human degenerative chondrocyte stress model.Zhonghua Guke Zazhi2018310655055529945412
     [Google Scholar]
  16. LiX.F. ZhangZ. WangT.B. Piezo1 protein mediates chondrocyte apoptosis through MAPK/ERK5 signaling pathway.Zhonghua Guke Zazhi20163612795803
     [Google Scholar]
  17. JiangL. ZhaoY. ChenW. The function of the novel mechanical activated ion channel Piezo1 in the human osteosarcoma cells.Med. Sci. Monit.2017235070508210.12659/MSM.90695929065102
     [Google Scholar]
  18. HuX. DuL. LiuS. LanZ. ZangK. FengJ. ZhaoY. YangX. XieZ. WangP.L. Ver HeulA.M. ChenL. SamineniV.K. WangY.Q. LavineK.J. GereauR.W.IV WuG.F. HuH. A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain.J. Clin. Invest.20231335e16150710.1172/JCI16150736701202
     [Google Scholar]
  19. YanZ. HeZ. JiangH. ZhangY. XuY. ZhangY. TRPV4-mediated mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via the Drp1-HK2 axis.Int. Immunopharmacol.202312311065110.1016/j.intimp.2023.11065137506502
     [Google Scholar]
  20. NagataK. HojoH. ChangS.H. OkadaH. YanoF. ChijimatsuR. OmataY. MoriD. MakiiY. KawataM. KanekoT. IwanagaY. NakamotoH. MaenoharaY. TachibanaN. IshikuraH. HiguchiJ. TaniguchiY. OhbaS. ChungU. TanakaS. SaitoT. Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development.Nat. Commun.2022131618710.1038/s41467‑022‑33744‑536261443
     [Google Scholar]
  21. Bay-JensenA.C. MobasheriA. ThudiumC.S. KrausV.B. KarsdalM.A. Blood and urine biomarkers in osteoarthritis – An update on cartilage associated type II collagen and aggrecan markers.Curr. Opin. Rheumatol.2022341546010.1097/BOR.000000000000084534652292
     [Google Scholar]
/content/journals/cmp/10.2174/0118761429317745241017114020
Loading
Repair Effect of siRNA Double Silencing of the Novel Mechanically Sensitive Ion Channels Piezo1 and TRPV4 on an Osteoarthritis Rat Model
Curr Mol Pharmacol 17, e18761429317745 (2024); https://doi.org/10.2174/0118761429317745241017114020
/content/journals/cmp/10.2174/0118761429317745241017114020
/content/journals/cmp/10.2174/0118761429317745241017114020
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Animal model; Collagen II; Osteoarthritis; Piezo1; siRNA; TRPV4

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test