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Kartogenin and Its Application in Regenerative Medicine

Current Medical Science volume 39, pages 16–20 (2019)Cite this article

Abstract

Regenerative medicine refers to the possibility of replacing aged/damaged cells with genetically similar young and functional cells to restore or establish normal function. Kartogenin (KGN), a small heterocyclic, drug-like compound was discovered in 2012, which is strongly associated with regenerative medicine. KGN has been applied in many regenerative fields, including cartilage regeneration and protection, tendon-bone healing, wound healing, and limb development. KGN could facilitate cartilage repair, promote formation of cartilage-like transition zone in tendon-bone junctions, stimulate collagen synthesis for wound healing, and regulate limb development in a coordinated manner. Considering the related mechanism, filamin A/CBFβ/RUNX1, Ihh, and TGFβ/Smad pathways have been reported to involve KGN. Therefore, KGN is proven a promising agent in regenerative medicine; however, studies conducted on the effect of KGN are limited to date and not convictive for long-term use. Further studies are recommended to explore the long-term effect and potential molecular mechanisms of KGN. Our investigations may motivate researchers to expand its applications in different forms and fields.

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References

  1. Kahn A. Regenerative medicine. J Soc Biol, 2001,195(1):5–7

    Article  CAS  PubMed  Google Scholar 

  2. Mason C, Dunnill P. A brief definition of regenerative medicine. Regen Med, 2008,3(1):1–5

    Article  PubMed  Google Scholar 

  3. Terzic A, Nelson TJ. Regenerative medicine advancing health care 2020. J Am Coll Cardiol, 2010,55(20):2254–2257

    Article  PubMed  Google Scholar 

  4. Hayek A, Kerstetter-Fogle AE, Sachlos E, et al. Kartogenin: a game-changer in regenerative medicine. Regen Med, 2012,7(4):475

    Article  CAS  PubMed  Google Scholar 

  5. Johnson K, Zhu S, Tremblay MS, et al. A stem cell-based approach to cartilage repair. Science, 2012,336(6082):717–721

    Article  CAS  Google Scholar 

  6. Marini JC, Forlino A. Replenishing cartilage from endogenous stem cells. N Engl J Med, 2012,366(26):2522–2524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kang ML, Ko JY, Kim JE, et al. Intra-articular delivery of kartogenin-conjugated chitosan nano/microparticles for cartilage regeneration. Biomaterials, 2014,35(37):9984–9994

    Article  CAS  PubMed  Google Scholar 

  8. Decker RS, Koyama E, Enomoto-Iwamoto M, et al. Mouse limb skeletal growth and synovial joint development are coordinately enhanced by Kartogenin. Dev Biol, 2014,395(2):255–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mohan G, Magnitsky S, Melkus G, et al. Kartogenin treatment prevented joint degeneration in a rodent model of osteoarthritis: A pilot study. J Orthop Res, 2016,34(10):1780–1789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu C, Li T, Yang Z, et al. Kartogenin Enhanced Chondrogenesis in Cocultures of Chondrocytes and Bone Mesenchymal Stem Cells. Tissue Eng Part A, 2018,24(11–12): 990–1000

    Article  CAS  PubMed  Google Scholar 

  11. Shi D, Xu X, Ye Y, et al. Photo-Cross-Linked Scaffold with Kartogenin-Encapsulated Nanoparticles for Cartilage Regeneration. ACS Nano, 2016,10(1):1292–1299

    Article  CAS  PubMed  Google Scholar 

  12. Lu HH, Thomopoulos S. Functional attachment of soft tissues to bone: development, healing, and tissue engineering. Annu Rev Biomed Eng, 2013,15:201–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Galatz LM, Sandell LJ, Rothermich SY, et al. Characteristics of the rat supraspinatus tendon during tendon-to-bone healing after acute injury. J Orthop Res, 2006,24(3):541–550

    Article  CAS  PubMed  Google Scholar 

  14. Rothrauff BB, Tuan RS. Cellular therapy in bone-tendon interface regeneration. Organogenesis, 2014,10(1):13–28

    Article  PubMed  Google Scholar 

  15. Zhang J, Wang JH. Kartogenin induces cartilage-like tissue formation in tendon-bone junction. Bone Res, 2014,2. ii: 14008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhou Y, Zhang J, Yang J, et al. Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface. J Tissue Eng Regen Med, 2017,11(12):3445–3456

    Article  CAS  PubMed  Google Scholar 

  17. Wang D, Tan H, Lebaschi AH, et al. Kartogenin Enhances Collagen Organization and Mechanical Strength of the Repaired Enthesis in a Murine Model of Rotator Cuff Repair. Arthroscopy, 2018,34(9): 2579–2587

    Article  PubMed  PubMed Central  Google Scholar 

  18. Martin P. Wound healing-aiming for perfect skin regeneration. Science, 1997,276(5309):75–81

    Article  CAS  PubMed  Google Scholar 

  19. Gibran NS, Boyce S, Greenhalgh DG. Cutaneous wound healing. J Burn Care Res, 2007,28(4):577–579

    Article  PubMed  Google Scholar 

  20. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med, 1999,341(10):738–746

    Article  CAS  PubMed  Google Scholar 

  21. Ruszczak Z. Effect of collagen matrices on dermal wound healing. Adv Drug Deliv Rev, 2003,55(12):1595–1611

    Article  CAS  PubMed  Google Scholar 

  22. Wang J, Zhou J, Zhang N, et al. A heterocyclic molecule kartogenin induces collagen synthesis of human dermal fibroblasts by activating the smad4/smad5 pathway. BiochemBiophys Res Commun, 2014,450(1):568–574

    Article  CAS  Google Scholar 

  23. Storm EE, Kingsley DM. GDF5 coordinates bone and joint formation during digit development. Dev Biol, 1999,209(1):11–27

    Article  CAS  PubMed  Google Scholar 

  24. Khan IM, Redman SN, Williams R, et al. The development of synovial joints. Curr Top Dev Biol, 2007,79:1–36

    Article  CAS  PubMed  Google Scholar 

  25. Holder N. An experimental investigation into the early development of the chick elbow joint. J Embryol Exp Morphol, 1977,39:115–127

    CAS  PubMed  Google Scholar 

  26. Ito MM, Kida MY. Morphological and biochemical reevaluation of the process of cavitation in the rat knee joint: cellular and cell strata alterations in the interzone. J Anat, 2000,197 Pt 4:659–679

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yoshida N, Ogata T, Tanabe K, et al. Filamin A-bound PEBP2beta/CBFbeta is retained in the cytoplasm and prevented from functioning as a partner of the Runx1 transcription factor. Mol Cell Biol, 2005,25(3):1003–1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kamekura S, Kawasaki Y, Hoshi K, et al. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Arthritis Rheum, 2006,54(8):2462–2470

    Article  CAS  PubMed  Google Scholar 

  29. Zheng Q, Zhou G, Morello R, et al. Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo. J Cell Biol, 2003,162(5):833–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wei J, Shimazu J, Makinistoglu MP, et al. Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. Cell, 2015,161(7):1576–1591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Minina E, Wenzel HM, Kreschel C, et al. BMP and Ihh/ PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation. Development, 2001, 128(22):4523–4534

    CAS  PubMed  Google Scholar 

  32. Kronenberg HM. Developmental regulation of the growth plate. Nature, 2003,423(6937):332–336

    Article  CAS  PubMed  Google Scholar 

  33. Tukachinsky H, Lopez LV, Salic A. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. J Cell Biol, 2010,191(2):415–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yang J, Andre P, Ye L, et al. The Hedgehog signalling pathway in bone formation. Int J Oral Sci, 2015,7(2):73–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Blaney Davidson EN, Vitters EL, van den Berg WB, et al. TGF beta-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7. Arthritis Res Ther, 2006,8(3):R65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Denis JF, Sader F, Gatien S, et al. Activation of Smad2 but not Smad3 is required to mediate TGF-beta signaling during axolotl limb regeneration. Development, 2016,143(19):3481–3490

    Article  CAS  PubMed  Google Scholar 

  37. Chong AK, Satterwhite T, Pham HM, et al. Live imaging of Smad2/3 signaling in mouse skin wound healing. Wound Repair Regen, 2007,15(5):762–766

    Article  PubMed  Google Scholar 

  38. Loiselle AE, Yukata K, Geary MB, et al. Development of antisense oligonucleotide (ASO) technology against Tgf-beta signaling to prevent scarring during flexor tendon repair. J Orthop Res, 2015,33(6):859–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Matsumoto Y, Otsuka F, Hino J, et al. Bone morphogenetic protein-3b (BMP-3b) inhibits osteoblast differentiation via Smad2/3 pathway by counteracting Smad1/5/8 signaling. Mol Cell Endocrinol, 2012,350(1):78–86

    Article  CAS  PubMed  Google Scholar 

  40. Nishida T, Kubota S, Aoyama E, et al. Impaired glycolytic metabolism causes chondrocyte hypertrophylike changes via promotion of phospho-Smad1/5/8 translocation into nucleus. Osteoarthritis Cartilage, 2013,21(5):700–709

    Article  CAS  PubMed  Google Scholar 

  41. van Caam A, Blaney Davidson E, Madej W, et al. Pronounced decrease in expreßsion of chondroprotective Smad2/3 phosphorylating TGFβ-signaling receptors during ageing in healthy cartilage. Osteoarthritis Cartilage, 2013,21(Suppl):S130

    Article  Google Scholar 

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Author notes

  1. These authors contributed equally to this work.

Affiliations

  1. Department of Sports Medicine, Fudan University, Shanghai, 200040, China

    Jiang-yu Cai, Jun Chen & Shi-yi Chen

  2. Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Li Zhang

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  1. Jiang-yu Cai
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  2. Li Zhang
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  3. Jun Chen
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  4. Shi-yi Chen
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Corresponding author

Correspondence to Shi-yi Chen.

Additional information

This study was funded by the National Key R&D Program of China (No. 2016YFC1100300, No. 2017YFC0840100 and No. 2017YFC0840106), the National Natural Science Foundation of China (No. 81572108 and No. 81772339), the Key Clinical Medicine Center of Shanghai (No. 2017ZZ01006), the Sanming Project of Medicine in Shenzhen (No. SZSM20161207), the Shanghai Rising Star Project (No. 18QB1400500), the Introduction Project of Clinical Medicine Expert Team for Suzhou (No. SZYJTD201714), CAS Key Laboratory of Nano-Bio Interface (No. 17NBI01) and State Key Laboratory of Molecular Engineering of Polymers (No. K2018-17).

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Cai, Jy., Zhang, L., Chen, J. et al. Kartogenin and Its Application in Regenerative Medicine. CURR MED SCI 39, 16–20 (2019). https://doi.org/10.1007/s11596-019-1994-6

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  • DOI: https://doi.org/10.1007/s11596-019-1994-6

Key words

  • kartogenin
  • regenerative medicine
  • mechanism