gene transfer techniques; genetic therapy; growth factors; interleukins; osteoarthritis; transcription factors; Medicine (all); General Medicine
Abstract :
[en] [en] OBJECTIVE: Osteoarthritis (OA) is the most common degenerative joint disease, characterized by a progressive loss of cartilage associated with synovitis and subchondral bone remodeling. There is however no treatment to cure or delay the progression of OA. The objective of this manuscript was to provide a scoping review of the preclinical and clinical studies reporting the effect of gene therapies for OA.
METHOD: This review followed the JBI methodology and was reported in accordance with the PRISMA-ScR checklist. All research studies that explore in vitro, in vivo, or ex vivo gene therapies that follow a viral or non-viral gene therapy approach were considered. Only studies published in English were included in this review. There were no limitations to their date of publication, country of origin, or setting. Relevant publications were searched in Medline ALL (Ovid), Embase (Elsevier), and Scopus (Elsevier) in March 2023. Study selection and data charting were performed by two independent reviewers.
RESULTS: We found a total of 29 different targets for OA gene therapy, including studies examining interleukins, growth factors and receptors, transcription factors and other key targets. Most articles were on preclinical in vitro studies (32 articles) or in vivo animal models (39 articles), while four articles were on clinical trials related to the development of TissueGene-C (TG-C).
CONCLUSION: In the absence of any DMOAD, gene therapy could be a highly promising treatment for OA, even though further development is required to bring more targets to the clinical stage.
Disciplines :
Rheumatology
Author, co-author :
Uebelhoer, Melanie; Artialis S.A., Liège, Belgium
Lambert, Cécile ; Université de Liège - ULiège > Département des Sciences de l'activité physique et de la réadaptation > musculoSkeletal Innovative research Lab (mSKIL)
Henrotin, Yves ; Université de Liège - ULiège > Département des Sciences de l'activité physique et de la réadaptation > Pathologie générale et physiopathologie - Techniques particulières de kinésithérapie ; Artialis S.A., Liège, Belgium ; Department of Physical Therapy and Rehabilitation, Princess Paola Hospital, Vivalia, Marche-en-Famenne, Belgium
Language :
English
Title :
Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review.
The authors would like to thank Dr. Nancy Durieux from the University of Liège—Research Unit for a life-Course perspective on Health and Education, Faculty of Psychology, Speech and Language Therapy and Educational Sciences for her help in setting up research strategies and their implementation into Covidence.
Lambert C Borderie D Dubuc J-E Rannou F Henrotin Y. Type II collagen peptide Coll2-1 is an actor of synovitis. Osteoarthr Cartil. (2019) 27:1680–91. 10.1016/j.joca.2019.07.00931325494
Loeser RF Goldring SR Scanzello CR Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. (2012) 64:1697–707. 10.1002/art.3445322392533
Lambert C Zappia J Sanchez C Florin A Dubuc J-E Henrotin Y. The damage-associated molecular patterns (DAMPs) as potential targets to treat osteoarthritis: perspectives from a review of the literature. Front Med. (2020) 7:607186. 10.3389/fmed.2020.60718633537330
Abramoff B Caldera FE. Osteoarthritis: pathology, diagnosis, and treatment options. Med Clin N Am. (2020) 104:293–311. 10.1016/j.mcna.2019.10.00732035570
Lewis R Gómez Álvarez CB Rayman M Lanham-New S Woolf A Mobasheri A. Strategies for optimising musculoskeletal health in the 21 st century. BMC Musculoskel Disord. (2019) 20:164. 10.1186/s12891-019-2510-730971232
Bannuru RR Osani MC Vaysbrot EE Arden NK Bennell K Bierma-Zeinstra SMA et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil. (2019) 27:1578–89. 10.1016/j.joca.2019.06.01131278997
Kolasinski SL Neogi T Hochberg MC Oatis C Guyatt G Block J et al. 2019 American college of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthrit Rheumatol. (2020) 72:220–33. 10.1002/art.4114231908163
Austine J Nair S Mirza K. Perspective of orthopedists on pain management in osteoarthritis: a qualitative study. Indian J Palliat Care. (2016) 22:410–5. 10.4103/0973-1075.19176427803562
Skou ST Roos EM. Physical therapy for patients with knee and hip osteoarthritis: supervised, active treatment is current best practice. Clin Exp Rheumatol. (2019) 37(Suppl. 120):112–7.33034560
Nelson AE Allen KD Golightly YM Goode AP Jordan JM. A systematic review of recommendations and guidelines for the management of osteoarthritis: The Chronic Osteoarthritis Management Initiative of the US Bone and Joint Initiative. Semin Arthritis Rheum. (2014) 43:701–12. 10.1016/j.semarthrit.2013.11.01224387819
Salem HS Ehiorobo JO Parvizi J Mont MA. The safety and efficacy of a novel cell-based gene therapy for knee osteoarthritis. Surg Technol Int. (2019) 35:370–6.31382315
Grässel S Muschter D. Recent advances in the treatment of osteoarthritis. F1000Research. (2020) 9:F1000. 10.12688/f1000research.22115.132419923
Grol MW Lee BH. Gene therapy for repair and regeneration of bone and cartilage. Curr Opin Pharmacol. (2018) 40:59–66. 10.1016/j.coph.2018.03.00529621661
Gantenbein B Tang S Guerrero J Higuita-Castro N Salazar-Puerta AI Croft AS et al. Non-viral gene delivery methods for bone and joints. Front Bioengin Biotechnol. (2020) 8:598466. 10.3389/fbioe.2020.59846633330428
Uzieliene I Kalvaityte U Bernotiene E Mobasheri A. Non-viral gene therapy for osteoarthritis. Front Bioeng Biotechnol. (2021) 8:618399. 10.3389/fbioe.2020.61839933520968
Pelletier JP Caron JP Evans C Robbins PD Georgescu HI Jovanovic D et al. In vivo suppression of early experimental osteoarthritis by interleukin- 1 receptor antagonist using gene therapy. Arthritis Rheum. (1997) 40:1012–9. 10.1002/art.17804006049182910
Baragi VM Renkiewicz RR Jordan H Bonadio J Hartman JW Roessler BJ. Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation. J Clin Invest. (1995) 96:2454–60. 10.1172/JCI1183037593634
Nixon AJ Grol MW Lang HM Ruan MZC Stone A Begum L et al. Disease-modifying osteoarthritis treatment with interleukin-1 receptor antagonist gene therapy in small and large animal models. Arthritis Rheumatol. (2018) 70:1757–68. 10.1002/art.4066830044894
Deng J Fukushima Y Nozaki K Nakanishi H Yada E Terai Y et al. Anti-inflammatory therapy for temporomandibular joint osteoarthritis using mRNA medicine encoding interleukin-1 receptor antagonist. Pharmaceutics. (2022) 14:1785. 10.3390/pharmaceutics1409178536145533
Senter R Boyce R Repic M Martin EW Chabicovsky M Langevin-Carpentier G et al. Efficacy and safety of FX201, a novel intra-articular IL-1Ra gene therapy for osteoarthritis treatment, in a rat model. Hum Gene Ther. (2022) 33:541–9. 10.1089/hum.2021.13134963343
Fernandes J Tardif G Martel-Pelletier J Lascau-Coman V Dupuis M Moldovan F et al. In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints. Prevention of osteoarthritis progression. Am J Pathol. (1999) 154:1159–69. 10.1016/S0002-9440(10)65368-010233854
Zhang X Yu C Xu S Zhang C Tang T Dai K. Direct chitosan-mediated gene delivery to the rabbit knee joints in vitro and in vivo. Biochem Biophys Res Commun. (2006) 341:202–8. 10.1016/j.bbrc.2005.12.17116413501
Deng RH Qiu B Zhou PH. Chitosan/hyaluronic acid/plasmid-DNA nanoparticles encoding interleukin-1 receptor antagonist attenuate inflammation in synoviocytes induced by interleukin-1 beta. J Mater Sci Mater Med. (2018) 29:155. 10.1007/s10856-018-6160-330276528
Frisbie DD Ghivizzani SC Robbins PD Evans CH McIlwraith CW. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther. (2002) 9:12–20. 10.1038/sj.gt.330160811850718
Goodrich LR Grieger JC Phillips JN Khan N Gray SJ McIlwraith CW et al. ScAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy. Gene Ther. (2015) 22:536–45. 10.1038/gt.2015.2125902762
Watson Levings RS Smith AD Broome TA Rice BL Gibbs EP Myara DA et al. Self-complementary adeno-associated virus-mediated interleukin-1 receptor antagonist gene delivery for the treatment of osteoarthritis: Test of efficacy in an equine model. Hum Gene Ther Clin Dev. (2018) 29:101–12. 10.1089/humc.2017.14329869535
Watson Levings RS Broome TA Smith AD Rice BL Gibbs EP Myara DA et al. Gene therapy for osteoarthritis: pharmacokinetics of intra-articular self-complementary adeno-associated virus interleukin-1 receptor antagonist delivery in an equine model. Hum Gene Ther Clin Dev. (2018) 29:90–100. 10.1089/humc.2017.14229869540
Glass KA Link JM Brunger JM Moutos FT Gersbach CA Guilak F. Tissue-engineered cartilage with inducible and tunable immunomodulatory properties. Biomaterials. (2014) 35:5921–31. 10.1016/j.biomaterials.2014.03.07324767790
Gabner S Ertl R Velde K Renner M Jenner F Egerbacher M et al. Cytokine-induced interleukin-1 receptor antagonist protein expression in genetically engineered equine mesenchymal stem cells for osteoarthritis treatment. J Gene Med. (2018) 20:e3021. 10.1002/jgm.302129608232
Chen B Qin J Wang H Magdalou J Chen L. Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits. Exp Mol Med. (2010) 42:684–95. 10.3858/emm.2010.42.10.06720733349
Zhang X Mao Z Yu C. Suppression of early experimental osteoarthritis by gene transfer of interleukin-1 receptor antagonist and interleukin-10. J Orthop Res. (2004) 22:742–50. 10.1016/j.orthres.2003.12.00715183429
Haupt JL Frisbie DD McIlwraith CW Robbins PD Ghivizzani S Evans CH et al. Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model. J Orthop Res. (2005) 23:118–26. 10.1016/j.orthres.2004.06.02015607883
Zhang P Zhong ZH Yu HT Liu B. Exogenous expression of IL-1Ra and TGF-β1 promotes in vivo repair in experimental rabbit osteoarthritis. Scand J Rheumatol. (2015) 44:404–11. 10.3109/03009742.2015.100994226079860
Wang HJ Yu CL Kishi H Motoki K Mao Z Bin et al. Suppression of experimental osteoarthritis by adenovirus-mediated double gene transfer. Chin Med J. (2006) 119:1365–73. 10.1097/00029330-200608020-0000916934183
Attur MG Dave MN Leung MY Cipolletta C Meseck M Woo SLC et al. Functional genomic analysis of type II IL-1β decoy receptor: potential for gene therapy in human arthritis and inflammation. J Immunol. (2002) 168:2001–10. 10.4049/jimmunol.168.4.200111823537
Broeren MGA de Vries M Bennink MB Arntz OJ van Lent PLEM van der Kraan PM et al. Suppression of the inflammatory response by disease-inducible interleukin-10 gene therapy in a three-dimensional micromass model of the human synovial membrane. Arthritis Res Ther. (2016) 18:186. 10.1186/s13075-016-1083-127519904
Farrell E Fahy N Ryan AE Flatharta CO O'Flynn L Ritter T et al. VIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis. Stem Cell Res Ther. (2016) 7:74. 10.1186/s13287-016-0331-227194025
Cameron AD Even KM Linardi RL Berglund AK Schnabel LV Engiles JB et al. Adeno-associated virus-mediated overexpression of interleukin-10 affects the immunomodulatory properties of equine bone marrow-derived mesenchymal stem cells. Hum Gene Ther. (2021) 32:907–18. 10.1089/hum.2020.31933843261
Watkins LR Chavez RA Landry R Fry M Green-Fulgham SM Coulson JD et al. Targeted interleukin-10 plasmid DNA therapy in the treatment of osteoarthritis: Toxicology and pain efficacy assessments. Brain Behav Immun. (2020) 90:155–66. 10.1016/j.bbi.2020.08.00532800926
Lang A Neuhaus J Pfeiffenberger M Schröder E Ponomarev I Weber Y et al. Optimization of a nonviral transfection system to evaluate Cox-2 controlled interleukin-4 expression for osteoarthritis gene therapy in vitro. J Gene Med. (2014) 16:352–63. 10.1002/jgm.281225382123
Song SY Hong J Go S Lim S Sohn HS Kang M et al. Interleukin-4 gene transfection and spheroid formation potentiate therapeutic efficacy of mesenchymal stem cells for osteoarthritis. Adv Healthc Mater. (2020) 9:1901612. 10.1002/adhm.20190161231977158
Broeren MGA Di Ceglie I Bennink MB van Lent PLEM van den Berg WB Koenders MI et al. Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation. PeerJ. (2018) 6:e4771. 10.7717/peerj.477129868252
Qiu B Xu XF Deng RH Xia GQ Shang XF Zhou PH. Hyaluronic acid-chitosan nanoparticles encoding CrmA attenuate interleukin-1β induced inflammation in synoviocytes in vitro. Int J Mol Med. (2019) 43:1076–84. 10.3892/ijmm.2018.399730483733
Attur MG Dave M Cipolletta C Kang P Goldring MB Patel IR et al. Reversal of autocrine and paracrine effects of interleukin 1 (IL-1) in human arthritis by type II IL-1 decoy receptor. Potential for pharmacological intervention. J Biol Chem. (2000) 275:40307–15. 10.1074/jbc.M00272120011007768
Manning K Rachakonda PS Rai MF Schmidt MFG. Co-expression of insulin-like growth factor-1 and interleukin-4 in an in vitro inflammatory model. Cytokine. (2010) 50:297–305. 10.1016/j.cyto.2010.01.01020188584
Weimer A Madry H Venkatesan JK Schmitt G Frisch J Wezel A et al. Benefits of recombinant adeno-associated virus (rAAV)-mediated insulinlike growth factor I (IGF-I) overexpression for the long-term reconstruction of human osteoarthritic cartilage by modulation of the IGF-I axis. Mol Med. (2012) 18:346–58. 10.2119/molmed.2011.0037122160392
Aguilar IN Trippel SB Shi S Bonassar LJ. Comparison of efficacy of endogenous and exogenous IGF-I in stimulating matrix production in neonatal and mature chondrocytes. Cartilage. (2015) 6:264–72. 10.1177/194760351557869126425264
Aguilar IN Trippel S Shi S Bonassar LJ. Customized biomaterials to augment chondrocyte gene therapy. Acta Biomater. (2017) 53:260–7. 10.1016/j.actbio.2017.02.00828185909
Ko JH Kang YM Yang JH Kim JS Lee WJ Kim SH et al. Regulation of MMP and TIMP expression in synovial fibroblasts from knee osteoarthritis with flexion contracture using adenovirus-mediated relaxin gene therapy. Knee. (2019) 26:317–29. 10.1016/j.knee.2019.01.01030770167
Ulrich-Vinther M Stengaard C Schwarz EM Goldring MB Soballe K. Adeno-associated vector mediated gene transfer of transforming growth factor - β1 to normal and osteoarthritic human chondrocytes stimulates cartilage anabolism. Eur Cells Mater. (2005) 10:40–50. 10.22203/eCM.v010a0516284937
Venkatesan JK Rey-Rico A Schmitt G Wezel A Madry H Cucchiarini M. rAAV-mediated overexpression of TGF-β stably restructures human osteoarthritic articular cartilage in situ. J Transl Med. (2013) 11:211. 10.1186/1479-5876-11-21124034904
Noh MJ Copeland RO Yi Y Choi KB Meschter C Hwang S et al. Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C). Cytotherapy. (2010) 12:384–93. 10.3109/1465324090347063920370350
Lee H Kim H Seo J Choi K Lee Y Park K et al. TissueGene-C promotes an anti-inflammatory micro-environment in a rat monoiodoacetate model of osteoarthritis via polarization of M2 macrophages leading to pain relief and structural improvement. Inflammopharmacology. (2020) 28:1237–52. 10.1007/s10787-020-00738-y32696209
Gao X Cheng H Awada H Tang Y Amra S Lu A et al. A comparison of BMP2 delivery by coacervate and gene therapy for promoting human muscle-derived stem cell-mediated articular cartilage repair. Stem Cell Res Ther. (2019) 10:346. 10.1186/s13287-019-1434-331771623
Matsumoto T Cooper GM Gharaibeh B Meszaros LB Li G Usas A et al. Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum. (2009) 60:1390–405. 10.1002/art.2444319404941
Tang R Harasymowicz NS Wu CL Collins KH Choi YR Oswald SJ et al. Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet–induced obesity. Sci Adv. (2020) 6:eaaz7492 10.1126/sciadv.aaz749232426485
Chen Z Deng S Yuan D Liu K Xiang X Cheng L et al. Novel nano-microspheres containing chitosan, hyaluronic acid, and chondroitin sulfate deliver growth and differentiation factor-5 plasmid for osteoarthritis gene therapy. J Zhejiang Univ Sci B. (2018) 19:910–23. 10.1631/jzus.B180009530507075
Antoniades HN Owen AJ. Growth factors and regulation of cell growth. Annu Rev Med. (1982) 33:445–63. 10.1146/annurev.me.33.020182.0023056282182
Ha CW Noh MJ Choi KB Lee KH. Initial phase i safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients. Cytotherapy. (2012) 14:247–56. 10.3109/14653249.2011.62964522242865
Cherian JJ Parvizi J Bramlet D Lee KH Romness DW Mont MA. Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-β1 in patients with grade 3 chronic degenerative joint disease of the knee. Osteoarthr Cartil. (2015) 23:2109–18. 10.1016/j.joca.2015.06.01926188189
Ha CW Cho JJ Elmallah RK Cherian JJ Kim TW Lee MC et al. A multicenter, single-blind, phase IIa clinical trial to evaluate the efficacy and safety of a cell-mediated gene therapy in degenerative knee arthritis patients. Hum Gene Ther Clin Dev. (2015) 26:125–30. 10.1089/humc.2014.14525760423
Kim MK Ha CW In Y Cho S Do Choi ES et al. A multicenter, double-blind, phase III clinical trial to evaluate the efficacy and safety of a cell and gene therapy in knee osteoarthritis patients. Hum Gene Ther Clin Dev. (2018) 29:48–59. 10.1089/humc.2017.24929641281
Sellon S Smith J De la Vega R Wisniewski S Jurisson M Scrabeck T et al. A phase I clinical trial of osteoarthritis gene therapy (NCT02790723). Mol Ther. (2022) 30:376.29641281
Kelley S Kivitz A Senter B Golod D Cinar A Martin E et al. Interim data from the first-in-human Phase 1 trial of FX201, an intra-articular, helper-dependent adenoviral gene therapy for osteoarthritis - safety, tolerability, biodistribution, and preliminary evaluationof clinical activity in 5 patients. Mol Ther. (2021) 29:288.
Cucchiarini M Terwilliger EF Kohn D Madry H. Remodelling of human osteoarthritic cartilage by FGF-2, alone or combined with Sox9 via rAAV gene transfer. J Cell Mol Med. (2009) 13:2476–88. 10.1111/j.1582-4934.2008.00474.x18705695
Daniels O Frisch J Venkatesan JK Rey-Rico A Schmitt G Cucchiarini M. Effects of raav-mediated sox9 overexpression on the biological activities of human osteoarthritic articular chondrocytes in their intrinsic three-dimensional environment. J Clin Med. (2019) 8:1637. 10.3390/jcm810163731591319
Tao K Rey-Rico A Frisch J Venkatesan JK Schmitt G Madry H et al. rAAV-mediated combined gene transfer and overexpression of TGF-β and SOX9 remodels human osteoarthritic articular cartilage. J Orthop Res. (2016) 34:2181–90. 10.1002/jor.2322826970525
Urich J Cucchiarini M Rey-Rico A. Therapeutic delivery of raav sox9 via polymeric micelles counteracts the effects of osteoarthritis-associated inflammatory cytokines in human articular chondrocytes. Nanomaterials. (2020) 10:1238. 10.3390/nano1006123832630578
Kawata M Teramura T Ordoukhanian P Head SR Natarajan P Sundaresan A et al. Krüppel-like factor-4 and Krüppel-like factor-2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis. Ann Rheum Dis. (2022). 10.1136/annrheumdis-2021-221867. [Epub ahead of print].35534137
Wang Y He SH Liang X Zhang XX Li SS Li TF. ATF4-modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy. IUBMB Life. (2021) 73:146–58. 10.1002/iub.241433249722
Fisch KM Gamini R Alvarez-Garcia O Akagi R Saito M Muramatsu Y et al. Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis. Osteoarthr Cartil. (2018) 26:1531–8. 10.1016/j.joca.2018.07.01230081074
Ruan MZC Dawson B Jiang M-M Gannon F Heggeness M Lee BHL. Quantitative imaging of murine osteoarthritic cartilage by phase-contrast micro-computed tomography. Arthritis Rheum. (2013) 65:388–96. 10.1002/art.3776623124630
Ruan MZC Cerullo V Cela R Clarke C Lundgren-Akerlund E Barry MA et al. Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes. Mol Ther Methods Clin Dev. (2016) 3:16008. 10.1038/mtm.2016.827626040
Stone A Grol MW Ruan MZC Dawson B Chen Y Jiang M-M et al. Combinatorial Prg4 and Il-1ra gene therapy protects against hyperalgesia and cartilage degeneration in post-traumatic osteoarthritis. Hum Gene Ther. (2019) 30:225–35. 10.1089/hum.2018.10630070147
Seol D Choe HH Zheng H Brouillette MJ Fredericks DC Petersen EB et al. Intra-articular adeno-associated virus-mediated proteoglycan 4 gene therapy for preventing posttraumatic osteoarthritis. Hum Gene Ther. (2022) 33:529–40. 10.1089/hum.2021.17734610749
Tashkandi M Ali F Alsaqer S Alhousami T Cano A Martin A et al. Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice. Int J Mol Sci. (2019) 20:4798. 10.3390/ijms2019479831569601
Venkatesan N Barré L Benani A Netter P Magdalou J Fournel-Gigleux S et al. Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: a strategy to promote cartilage repair. Proc Natl Acad Sci USA. (2004) 101:18087–92. 10.1073/pnas.040450410215601778
Fu X Qiu R Tang C Wang X Cheng X Yin M. Effects of GGCX overexpression on anterior cruciate ligament transection-induced osteoarthritis in rabbits. Mol Med Rep. (2018) 17:3821–8. 10.3892/mmr.2017.830429257344
Hsieh JL Shen PC Shiau AL Jou IM Lee CH Teo ML et al. Adenovirus-mediated kallistatin gene transfer ameliorates disease progression in a rat model of osteoarthritis induced by anterior cruciate ligament transection. Hum Gene Ther. (2009) 20:147–58. 10.1089/hum.2008.09620377366
Ashraf S Kim BJ Park S Park H Lee SH. RHEB gene therapy maintains the chondrogenic characteristics and protects cartilage tissue from degenerative damage during experimental murine osteoarthritis. Osteoarthr Cartil. (2019) 27:1508–17. 10.1016/j.joca.2019.05.02431229684
Grossin L Cournil-Henrionnet C Pinzano A Gaborit N Dumas D Etienne S et al. Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis. FASEB J. (2006) 20:65–75. 10.1096/fj.04-2889com16394269
Yoon DS Lee K-M Choi Y Ko EA Lee N-H Cho S et al. TLR4 downregulation by the RNA-binding protein PUM1 alleviates cellular aging and osteoarthritis. Cell Death Differ. (2022) 29:1364–78. 10.1038/s41418-021-00925-635190709
Na HS Lee S-Y Lee DH Woo JS Choi S-Y Cho K-H et al. Soluble CCR2 gene therapy controls joint inflammation, cartilage damage, and the progression of osteoarthritis by targeting MCP-1 in a monosodium iodoacetate (MIA)-induced OA rat model. J Transl Med. (2022) 20:428. 10.1186/s12967-022-03515-336138477
Cao C Shi Y Zhang X Li Q Zhang J Zhao F et al. Cholesterol-induced LRP3 downregulation promotes cartilage degeneration in osteoarthritis by targeting Syndecan-4. Nat Commun. (2022) 13:7139. 10.1038/s41467-022-34830-436414669
Dong Q Wei L Zhang MQ Wang X. Regulatory RNA binding proteins contribute to the transcriptome-wide splicing alterations in human cellular senescence. Aging. (2018) 10:1489–505. 10.18632/aging.10148529936497
Wojdasiewicz P Poniatowski ŁA Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediat Inflamm. (2014) 2014:561459. 10.1155/2014/56145924876674
Lara-Castillo N Johnson ML LRP. receptor family member associated bone disease. Rev Endocr Metab Disord. (2015) 16:141–8. 10.1007/s11154-015-9315-226048454
Zhao L Huang J Fan Y Li J You T He S et al. Exploration of CRISPR/Cas9-based gene editing as therapy for osteoarthritis. Ann Rheum Dis. (2019) 78:676–82. 10.1136/annrheumdis-2018-21472430842121
