Kartogenin对软骨再生作用的研究进展
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摘要
目的综述小分子化合物kartogenin(KGN)在骨性关节炎(osteoarthritis,OA)治疗中对抑制软骨退变及促进软骨再生的研究进展。方法广泛查阅近年来KGN对OA治疗作用研究进展的相关文献。结果 KGN可以改善软骨代谢的微环境,促进软骨合成代谢中软骨标志物的表达。KGN已经用于促进软骨再生的软骨组织工程研究中,通过与不同的材料结合,可以提高对软骨的保护作用,并促进软骨细胞的形成。结论 KGN可以促进间充质干细胞向软骨细胞的分化,抑制OA疾病的进程,望成为一种OA疾病调修药物,但仍需进一步研究。
Objective To review the research progress of small molecule compound kartogenin(KGN) in inhibiting cartilage degeneration and cartilage regeneration in the treatment of osteoarthritis(OA). Methods A wide range of literatures on the research progress of KGN in the treatment of OA in recent years were extensively reviewed. Results KGN can improve the microenvironment of cartilage metabolism and promote the expression of cartilage markers in cartilage anabolism. New cartilage tissue engineering methods using KGN have emerged, including the incorporation of KGN into natural or synthetic three-dimensional porous materials, or the development of hydrogels in which KGN is combined with biodegradable materials. Conclusion KGN is expected to be an OA disease-modifying drug, but first of all, it should be clear about its most suitable amount in the basic research, the form of administration, biological toxicity and its mechanism of action in inhibiting the occurrence and development of OA.
Objective To review the research progress of small molecule compound kartogenin(KGN) in inhibiting cartilage degeneration and cartilage regeneration in the treatment of osteoarthritis(OA). Methods A wide range of literatures on the research progress of KGN in the treatment of OA in recent years were extensively reviewed. Results KGN can improve the microenvironment of cartilage metabolism and promote the expression of cartilage markers in cartilage anabolism. New cartilage tissue engineering methods using KGN have emerged, including the incorporation of KGN into natural or synthetic three-dimensional porous materials, or the development of hydrogels in which KGN is combined with biodegradable materials. Conclusion KGN is expected to be an OA disease-modifying drug, but first of all, it should be clear about its most suitable amount in the basic research, the form of administration, biological toxicity and its mechanism of action in inhibiting the occurrence and development of OA.
引文
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[8]Miyatake K, Iwasa K, Mcnary SM, et al. Modulation of Superficial Zone Protein/lubricin/PRG4 by Kartogenin and Transforming Growth Factorbeta1 in Surface Zone Chondrocytes in Bovine Articular Cartilage[J].Cartilage,2016, 7(4):388-397.
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[10]Valiania,Izadi MA,Bahrahian H,et al.Comparison between the effect of kartogenin and TGF-β3 on chondrogenesis of human adipose-derived stem cells in fibrin scaffold[J]. Bratislavske lekarske listy,2017,118(10):591-597.
[11]Spakova T,Plsikova J,Harvanova D,et al.Influence of Kartogenin on Chondrogenic Differentiation of Human Bone Marrow-Derived MSCs in 2D Culture and in Co-Cultivation with OA Osteochondral Explant[J]. Molecules(Basel, Switzerland),2018, 23(1):181
[12]Zhang Y,Li P,Wang H,et al.Research progress on reconstruction of meniscus in tissue engineering[J].The Journal of sports medicine and physical fitness,2017, 57(5):595-603.
[13]Huang H,Xu H,Zhao J.A Novel Approach for Meniscal Regeneration Using Kartogenin-Treated Autologous Tendon Graft[J].The American journal of sports medicine,2017,45(14):3289-3297.
[14]Zhang J,Yuan T,Zheng N,et al.The combined use of kartogenin and plateletrich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses[J]. Bone&joint research,2017,6(4):231-244.
[15]Zhou Y,Zhang J,Yang J,et al.Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface[J].Journal of tissue engineering and regenerative medicine,2017,11(12):3445-3456.
[16]Mardones R,Jofre CM,Minguell JJ.Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration[J]. International journal of stem cells, 2015, 8(1):48-53.
[17]Li X, Ding J, Zhuang X, et al. Chitosan-Based Scaffolds for Cartilage Regeneration[M]. 2016:61-82
[18]Sun X, Wang J, Wang Y, et al. Collagen-based porous scaffolds containing PLGA microspheres for controlled kartogenin release in cartilage tissue engineering[J]. Artificial cells, nanomedicine, and biotechnology,2017,591(12):1-10.
[19]Liu C, Li T, Yang Z, et al. Kartogenin Enhanced Chondrogenesis in Cocultures of Chondrocytes and Bone Mesenchymal Stem Cells[J]. Tissue engineering Part A, 2018, 24(11-12):990-1000.
[20]Shi D, Xu X, Ye Y, et al. Photo-Cross-Linked Scaffold with KartogeninEncapsulated Nanoparticles for Cartilage Regeneration[J]. ACS nano, 2016,10(1):1292-1299.
[21]Kang ML, Jeong SY, Im GI. Hyaluronic Acid Hydrogel Functionalized with Self-Assembled Micelles of Amphiphilic PEGylated Kartogenin for the Treatment of Osteoarthritis[J]. Tissue engineering Part A, 2017, 23(13-14):630-639.
[22]Hu Q, Ding B, Yan X, et al. Polyethylene glycol modified PAMAM dendrimer delivery of kartogenin to induce chondrogenic differentiation of mesenchymal stem cells[J]. Nanomedicine:nanotechnology, biology, and medicine, 2017, 13(7):2189-2198.
[23]Maudens P, Seemayer C A, Thauvin C, et al. Nanocrystal-Polymer Particles:Extended Delivery Carriers for Osteoarthritis Treatment[J].2018,14(8).
[24]Fan W, Li J, Yuan L, et al. Intra-articular injection of kartogenin-conjugated polyurethane nanoparticles attenuates the progression of osteoarthritis[J].Drug delivery, 2018, 25(1):1004-1012.
[2]Madry H, Cucchiarini M. Tissue-engineering strategies to repair joint tissue in osteoarthritis:nonviral gene-transfer approaches[J]. Current rheumatology reports, 2014, 16(10):450.
[3]Van Der Kraan PM, Van Den Berg WB. Osteophytes:relevance and biology[J].Osteoarthritis and cartilage,2007,15(3):237-244.
[4]Elford PR,Graeber M,Ohtsu H,et al.Induction of swelling, synovial hyperplasia and cartilage proteoglycan loss upon intra-articular injection of transforming growth factor beta-2 in the rabbit[J].Cytokine,1992,4(3):232-238.
[5]Li X,Ding J,Zhang Z,et al.Kartogenin-Incorporated Thermogel Supports Stem Cells for Significant Cartilage Regeneration[J]. ACS applied materials&interfaces,2016, 8(8):5148-5159.
[6]Jones AR,Gleghorn JP,Hughes CE,et al.Binding and localization of recombinant lubricin to articular cartilage surfaces[J]. Journal of orthopaedic research:official publication of the Orthopaedic Research Society, 2007,25(3):283-292.
[7]Liu C, Ma X, Li T, et al. Kartogenin, transforming growth factor-beta1 and bone morphogenetic protein-7 coordinately enhance lubricin accumulation in bone-derived mesenchymal stem cells[J]. Cell biology international,2015,39(9):1026-1035.
[8]Miyatake K, Iwasa K, Mcnary SM, et al. Modulation of Superficial Zone Protein/lubricin/PRG4 by Kartogenin and Transforming Growth Factorbeta1 in Surface Zone Chondrocytes in Bovine Articular Cartilage[J].Cartilage,2016, 7(4):388-397.
[9]Ude CC, Shamsul BS, Ng MH, et al. Long-term evaluation of osteoarthritis sheep knee, treated with TGF-β3 and BMP-6 induced multipotent stem cells[J]. Experimental gerontology,2018,104:43-51.
[10]Valiania,Izadi MA,Bahrahian H,et al.Comparison between the effect of kartogenin and TGF-β3 on chondrogenesis of human adipose-derived stem cells in fibrin scaffold[J]. Bratislavske lekarske listy,2017,118(10):591-597.
[11]Spakova T,Plsikova J,Harvanova D,et al.Influence of Kartogenin on Chondrogenic Differentiation of Human Bone Marrow-Derived MSCs in 2D Culture and in Co-Cultivation with OA Osteochondral Explant[J]. Molecules(Basel, Switzerland),2018, 23(1):181
[12]Zhang Y,Li P,Wang H,et al.Research progress on reconstruction of meniscus in tissue engineering[J].The Journal of sports medicine and physical fitness,2017, 57(5):595-603.
[13]Huang H,Xu H,Zhao J.A Novel Approach for Meniscal Regeneration Using Kartogenin-Treated Autologous Tendon Graft[J].The American journal of sports medicine,2017,45(14):3289-3297.
[14]Zhang J,Yuan T,Zheng N,et al.The combined use of kartogenin and plateletrich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses[J]. Bone&joint research,2017,6(4):231-244.
[15]Zhou Y,Zhang J,Yang J,et al.Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface[J].Journal of tissue engineering and regenerative medicine,2017,11(12):3445-3456.
[16]Mardones R,Jofre CM,Minguell JJ.Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration[J]. International journal of stem cells, 2015, 8(1):48-53.
[17]Li X, Ding J, Zhuang X, et al. Chitosan-Based Scaffolds for Cartilage Regeneration[M]. 2016:61-82
[18]Sun X, Wang J, Wang Y, et al. Collagen-based porous scaffolds containing PLGA microspheres for controlled kartogenin release in cartilage tissue engineering[J]. Artificial cells, nanomedicine, and biotechnology,2017,591(12):1-10.
[19]Liu C, Li T, Yang Z, et al. Kartogenin Enhanced Chondrogenesis in Cocultures of Chondrocytes and Bone Mesenchymal Stem Cells[J]. Tissue engineering Part A, 2018, 24(11-12):990-1000.
[20]Shi D, Xu X, Ye Y, et al. Photo-Cross-Linked Scaffold with KartogeninEncapsulated Nanoparticles for Cartilage Regeneration[J]. ACS nano, 2016,10(1):1292-1299.
[21]Kang ML, Jeong SY, Im GI. Hyaluronic Acid Hydrogel Functionalized with Self-Assembled Micelles of Amphiphilic PEGylated Kartogenin for the Treatment of Osteoarthritis[J]. Tissue engineering Part A, 2017, 23(13-14):630-639.
[22]Hu Q, Ding B, Yan X, et al. Polyethylene glycol modified PAMAM dendrimer delivery of kartogenin to induce chondrogenic differentiation of mesenchymal stem cells[J]. Nanomedicine:nanotechnology, biology, and medicine, 2017, 13(7):2189-2198.
[23]Maudens P, Seemayer C A, Thauvin C, et al. Nanocrystal-Polymer Particles:Extended Delivery Carriers for Osteoarthritis Treatment[J].2018,14(8).
[24]Fan W, Li J, Yuan L, et al. Intra-articular injection of kartogenin-conjugated polyurethane nanoparticles attenuates the progression of osteoarthritis[J].Drug delivery, 2018, 25(1):1004-1012.