Polydeoxyribonucleotide ameliorates IL-1β-induced impairment of chondrogenic differentiation in human bone marrow-derived mesenchymal stem cells.
Humans
Mesenchymal Stem Cells
/ metabolism
Polydeoxyribonucleotides
/ pharmacology
Interleukin-1beta
/ metabolism
Chondrogenesis
/ drug effects
Cell Differentiation
/ drug effects
Signal Transduction
/ drug effects
Cells, Cultured
Osteoarthritis
/ metabolism
Cyclic AMP
/ metabolism
NF-kappa B
/ metabolism
Chondrocytes
/ metabolism
Cytokines
/ metabolism
Apoptosis
/ drug effects
Chondrogenic differentiation
Interleukin-1β
Mesenchymal stem cell
Osteoarthritis
Polydeoxyribonucleotide
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 10 2024
30 10 2024
Historique:
received:
24
01
2024
accepted:
21
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
Osteoarthritis (OA) is a degenerative disease of the joints, prevalent worldwide. Polydeoxyribonucleotide (PDRN) is used for treating knee OA. However, the role of PDRN in IL-1β-induced inflammatory responses in human bone marrow-derived mesenchymal stem cells (hBMSCs) remains unknown. Here, we investigated the role of PDRN in IL-1β-induced impairment of chondrogenic differentiation in hBMSCs. hBMSCs treated with PDRN showed a large micromass, enhanced safranin O and alcian blue staining intensity, and increased expression of chondrogenic genes in IL-1β-induced inflammatory responses, in addition to regulation of catabolic and anabolic genes. In addition, PDRN treatment suppressed the expression of inflammatory cytokines and mitigated IL-1β-induced apoptosis in hBMSCs. Mechanistically, PDRN treatment increased the formation of cyclic adenosine monophosphate (cAMP) and upregulated the phosphorylation of cAMP-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) through the adenosine A2A receptor in hBMSCs and thus blocked the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Thus, IL-1β-induced expression of inflammatory cytokines in hBMSCs was directly reduced by adenosine A2A receptor activation. Based on our results, we suggest that PDRN may be a promising MSC-based therapeutic agent for OA.
Identifiants
pubmed: 39478005
doi: 10.1038/s41598-024-77264-2
pii: 10.1038/s41598-024-77264-2
doi:
Substances chimiques
Polydeoxyribonucleotides
0
Interleukin-1beta
0
Cyclic AMP
E0399OZS9N
NF-kappa B
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26076Subventions
Organisme : National Research Foundation of Korea
ID : 2021R1A6A3A01086535
Organisme : National Research Foundation of Korea
ID : 2022R1I1A1A01065666
Organisme : National Research Foundation of Korea
ID : 2021R1F1A1062829
Organisme : EMBRI Grants
ID : Grants 2021-EMBRISN0006
Organisme : the Korean Fund for Regenerative Medicine
ID : 21A0202L1 and 21C0715L1
Organisme : Korean Health Technology R&D Project
ID : HI21C1314 and HI22C1588
Informations de copyright
© 2024. The Author(s).
Références
Felson, D. T. et al. Osteoarthritis: New insights. Part 1: The disease and its risk factors. Ann. Intern. Med. 133, 635–646 (2000).
pubmed: 11033593
doi: 10.7326/0003-4819-133-8-200010170-00016
Katz, J. N., Arant, K. R. & Loeser, R. F. Diagnosis and treatment of hip and knee osteoarthritis: A review. JAMA 325, 568–578 (2021).
pubmed: 33560326
pmcid: 8225295
doi: 10.1001/jama.2020.22171
Osteoarthritis A Serious Disease, Submitted to the U.S. Food and Drug Administration. (2016).
Wojdasiewicz, P., Poniatowski, L. A. & Szukiewicz, D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediat. Inflamm. 561459 (2014).
Freitag, J. et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: Reparative pathways, safety and efficacy - a review. BMC Musculoskelet. Disord. 17, 230 (2016).
pubmed: 27229856
pmcid: 4880954
doi: 10.1186/s12891-016-1085-9
Xiang, X. N. et al. Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis. Stem Cell. Res. Ther. 13, 14 (2022).
pubmed: 35012666
pmcid: 8751117
doi: 10.1186/s13287-021-02689-9
Pers, Y. M., Ruiz, M., Noel, D. & Jorgensen, C. Mesenchymal stem cells for the management of inflammation in osteoarthritis: State of the art and perspectives. Osteoarthr. Cartil. 23, 2027–2035 (2015).
doi: 10.1016/j.joca.2015.07.004
Pittenger, M. F. et al. Mesenchymal stem cell perspective: Cell biology to clinical progress. NPJ Regen. Med. 4, 22 (2019).
pubmed: 31815001
pmcid: 6889290
doi: 10.1038/s41536-019-0083-6
Lee, K. B., Hui, J. H., Song, I. C., Ardany, L. & Lee, E. H. Injectable mesenchymal stem cell therapy for large cartilage defects–a porcine model. Stem Cells. 25, 2964–2971 (2007).
pubmed: 17656639
doi: 10.1634/stemcells.2006-0311
Sato, M. et al. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res. Ther. 14, R31 (2012).
pubmed: 22314040
pmcid: 3392826
doi: 10.1186/ar3735
Lamo-Espinosa, J. M. et al. Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis. J. Transl. Med. 18, 356 (2020).
pubmed: 32948200
pmcid: 7501623
doi: 10.1186/s12967-020-02530-6
Wang, A. T., Feng, Y., Jia, H. H., Zhao, M. & Yu, H. Application of mesenchymal stem cell therapy for the treatment of osteoarthritis of the knee: A concise review. World J. Stem Cells 11, 222–235 (2019).
pubmed: 31110603
pmcid: 6503460
doi: 10.4252/wjsc.v11.i4.222
Huh, J. E. et al. Mangiferin reduces the inhibition of chondrogenic differentiation by IL-1beta in mesenchymal stem cells from subchondral bone and targets multiple aspects of the smad and SOX9 pathways. Int. J. Mol. Sci. 15, 16025–16042 (2014).
pubmed: 25216336
pmcid: 4200868
doi: 10.3390/ijms150916025
Gao, B. et al. Melatonin rescued interleukin 1beta-impaired chondrogenesis of human mesenchymal stem cells. Stem Cell. Res. Ther. 9, 162 (2018).
pubmed: 29898779
pmcid: 6001057
doi: 10.1186/s13287-018-0892-3
Pattappa, G. et al. Physioxia Has a beneficial effect on cartilage matrix production in interleukin-1 beta-inhibited mesenchymal stem cell chondrogenesis. Cells-Basel 8, (2019).
Bhogoju, S., Khan, S. & Subramanian, A. Continuous low-intensity ultrasound preserves chondrogenesis of mesenchymal stromal cells in the presence of cytokines by inhibiting NFkappaB activation. Biomolecules 12 (2022).
Baek, A., Kim, Y., Lee, J. W., Lee, S. C. & Cho, S. R. Effect of polydeoxyribonucleotide on angiogenesis and wound healing in an in vitro model of osteoarthritis. Cell. Transpl. 27, 1623–1633 (2018).
doi: 10.1177/0963689718804130
Baek, A., Kim, M., Kim, S. H., Cho, S. R. & Kim, H. J. Anti-inflammatory effect of DNA polymeric molecules in a cell model of osteoarthritis. Inflammation 41, 677–688 (2018).
pubmed: 29302765
doi: 10.1007/s10753-017-0722-2
Jeong, W. et al. Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model. Int. J. Mol. Sci. 18, (2017).
Lee, D. W., Hong, H. J., Roh, H. & Lee, W. J. The effect of polydeoxyribonucleotide on ischemic rat skin flap survival. Ann. Plast. Surg. 75, 84–90 (2015).
pubmed: 25954843
doi: 10.1097/SAP.0000000000000053
Kim, M. S., Cho, R. K. & In, Y. The efficacy and safety of polydeoxyribonucleotide for the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. Medicine (Baltim). 98, e17386 (2019).
doi: 10.1097/MD.0000000000017386
Lee, D. O., Yoo, J. H., Cho, H. I., Cho, S. & Cho, H. R. Comparing effectiveness of polydeoxyribonucleotide injection and corticosteroid injection in plantar fasciitis treatment: A prospective randomized clinical study. Foot Ankle Surg. 26, 657–661 (2020).
pubmed: 31521520
doi: 10.1016/j.fas.2019.08.005
Ko, I. G. et al. Adenosine A2A receptor agonist polydeoxyribonucleotide ameliorates short-term memory impairment by suppressing cerebral ischemia-induced inflammation via MAPK pathway. PLoS One. 16, e0248689 (2021).
pubmed: 33735236
pmcid: 7971468
doi: 10.1371/journal.pone.0248689
Sun, C., Wang, B. & Hao, S. Adenosine-A2A receptor pathway in cancer immunotherapy. Front. Immunol. 13, 837230 (2022).
pubmed: 35386701
pmcid: 8977492
doi: 10.3389/fimmu.2022.837230
Rho, J. H. et al. Polydeoxyribonucleotide ameliorates inflammation and apoptosis in achilles tendon-injury rats. Int. Neurourol. J. 24, 79–87 (2020).
pubmed: 33271004
pmcid: 7731881
doi: 10.5213/inj.2040428.214
Lee, S., Won, K. Y. & Joo, S. Protective effect of polydeoxyribonucleotide against CCl4-induced acute liver injury in mice. Int. Neurourol. J. 24, 88–95 (2020).
pubmed: 33271005
pmcid: 7731878
doi: 10.5213/inj.2040430.215
Ko, I. G. et al. Adenosine A(2A) receptor agonist polydeoxyribonucleotide alleviates interstitial cystitis-Induced Voiding Dysfunction by suppressing inflammation and apoptosis in rats. J. Inflamm. Res. 14, 367–378 (2021).
pubmed: 33623409
pmcid: 7894910
doi: 10.2147/JIR.S287346
Kwon, D. R., Park, G. Y. & Lee, S. C. Treatment of full-thickness rotator cuff tendon tear using umbilical cord blood-derived mesenchymal stem cells and polydeoxyribonucleotides in a rabbit model. Stem Cells Int. 7146384 (2018).
Kwon, D. R., Park, G. Y., Moon, Y. S. & Lee, S. C. Therapeutic effects of umbilical cord blood-derived mesenchymal stem cells combined with polydeoxyribonucleotides on full-thickness Rotator Cuff Tendon tear in a rabbit model. Cell. Transpl. 27, 1613–1622 (2018).
doi: 10.1177/0963689718799040
Kim, D. S. et al. Advanced PLGA hybrid scaffold with a bioactive PDRN/BMP2 nanocomplex for angiogenesis and bone regeneration using human fetal MSCs. Sci. Adv. 7, eabj1083 (2021).
pubmed: 34878837
pmcid: 8654289
doi: 10.1126/sciadv.abj1083
Lim, H. K. et al. Bone regeneration in ceramic scaffolds with variable concentrations of PDRN and rhBMP-2. Sci. Rep. 11, 11470 (2021).
pubmed: 34075179
pmcid: 8169763
doi: 10.1038/s41598-021-91147-w
Kim, S. K., Huh, C. K., Lee, J. H., Kim, K. W. & Kim, M. Y. Histologic study of bone-forming capacity on polydeoxyribonucleotide combined with demineralized dentin matrix. Maxillofac. Plast. Reconstr. Surg. 38, 7 (2016).
pubmed: 26913276
pmcid: 4752573
doi: 10.1186/s40902-016-0053-5
Kim, D. S. et al. Promotion of Bone Regeneration using Bioinspired PLGA/MH/ECM Scaffold Combined with Bioactive PDRN. Mater. (Basel) 14 (2021).
Lee, H. Y. et al. Multi-modulation of immune-inflammatory response using bioactive molecule-integrated PLGA composite for spinal fusion. Mater. Today Bio. 19, 100611 (2023).
pubmed: 36969699
pmcid: 10034518
doi: 10.1016/j.mtbio.2023.100611
Bitto, A. et al. Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A((2)A) receptor. Arthritis Rheum. 63, 3364–3371 (2011).
pubmed: 21769841
doi: 10.1002/art.30538
Picciolo, G. et al. PDRN, a natural bioactive compound, blunts inflammation and positively reprograms healing genes in an in vitro model of oral mucositis. Biomed. Pharmacother. 138, 111538 (2021).
pubmed: 34311536
doi: 10.1016/j.biopha.2021.111538
Baek, D. et al. Inhibition of miR-449a promotes cartilage regeneration and prevents progression of Osteoarthritis in in vivo rat models. Mol. Ther. Nucleic Acids. 13, 322–333 (2018).
pubmed: 30326428
pmcid: 6197768
doi: 10.1016/j.omtn.2018.09.015
Lee, S. et al. microRNA-495 inhibits chondrogenic differentiation in human mesenchymal stem cells by targeting Sox9. Stem Cells Dev. 23, 1798–1808 (2014).
pubmed: 24654627
pmcid: 4103260
doi: 10.1089/scd.2013.0609
Choi, S. M. et al. Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel. Cell. Death Dis. 9, 866 (2018).
pubmed: 30158625
pmcid: 6115405
doi: 10.1038/s41419-018-0914-1
Eggerschwiler, B., Canepa, D. D., Pape, H. C., Casanova, E. A. & Cinelli, P. Automated digital image quantification of histological staining for the analysis of the trilineage differentiation potential of mesenchymal stem cells. Stem Cell. Res. Ther. 10, 69 (2019).
pubmed: 30808403
pmcid: 6390603
doi: 10.1186/s13287-019-1170-8
Yang, D., Cao, G., Ba, X. & Jiang, H. Epigallocatechin-3-O-gallate promotes extracellular matrix and inhibits inflammation in IL-1beta stimulated chondrocytes by the PTEN/miRNA-29b pathway. Pharm. Biol. 60, 589–599 (2022).
pubmed: 35260041
pmcid: 8920401
doi: 10.1080/13880209.2022.2039722
Squadrito, F. et al. Pharmacological activity and clinical use of PDRN. Front. Pharmacol. 8, 224 (2017).
pubmed: 28491036
pmcid: 5405115
doi: 10.3389/fphar.2017.00224
Colangelo, M. T., Galli, C. & Guizzardi, S. Polydeoxyribonucleotide regulation of inflammation. Adv. Wound Care. 9, 576–589 (2020).
doi: 10.1089/wound.2019.1031
Sini, P. et al. Effect of polydeoxyribonucleotides on human fibroblasts in primary culture. Cell. Biochem. Funct. 17, 107–114 (1999).
pubmed: 10377956
doi: 10.1002/(SICI)1099-0844(199906)17:2<107::AID-CBF815>3.0.CO;2-#
Hwang, L. et al. Attenuation effect of polydeoxyribonucleotide on inflammatory cytokines and apoptotic factors induced by particulate matter (PM10) damage in human bronchial cells. J. Biochem. Mol. Toxicol. 35, e22635 (2021).
pubmed: 32985769
doi: 10.1002/jbt.22635
Sun, W. et al. Caffeic acid phenethyl ester attenuates osteoarthritis progression by activating NRF2/HO–1 and inhibiting the NF–kappaB signaling pathway. Int. J. Mol. Med. 50 (2022).
Yuan, G. et al. RGS12 is a Novel critical NF-kappaB activator in inflammatory arthritis. iScience. 23, 101172 (2020).
pubmed: 32512384
pmcid: 7281782
doi: 10.1016/j.isci.2020.101172
Dalle Carbonare, L. et al. Methylsulfonylmethane enhances MSC chondrogenic commitment and promotes pre-osteoblasts formation. Stem Cell. Res. Ther. 12, 326 (2021).
pubmed: 34090529
doi: 10.1186/s13287-021-02396-5
Bahrampour Juybari, K., Kamarul, T., Najafi, M., Jafari, D. & Sharifi, A. M. Restoring the IL-1beta/NF-kappaB-induced impaired chondrogenesis by diallyl disulfide in human adipose-derived mesenchymal stem cells via attenuation of reactive oxygen species and elevation of antioxidant enzymes. Cell. Tissue Res. 373, 407–419 (2018).
pubmed: 29582166
doi: 10.1007/s00441-018-2825-y
Wu, H., Yin, Z., Wang, L., Li, F. & Qiu, Y. Honokiol improved chondrogenesis and suppressed inflammation in human umbilical cord derived mesenchymal stem cells via blocking nuclear factor-kappab pathway. BMC Cell. Biol. 18, 29 (2017).
pubmed: 28851291
pmcid: 5576244
doi: 10.1186/s12860-017-0145-9
Lei, M., Liu, S. Q. & Liu, Y. L. Resveratrol protects bone marrow mesenchymal stem cell derived chondrocytes cultured on chitosan-gelatin scaffolds from the inhibitory effect of interleukin-1beta. Acta Pharmacol. Sin. 29, 1350–1356 (2008).
pubmed: 18954530
doi: 10.1111/j.1745-7254.2008.00880.x
Ai, Y. et al. Purine and purinergic receptors in health and disease. MedComm (2020). 4, e359 (2023).
pubmed: 37692109
doi: 10.1002/mco2.359
Guizzardi, S. et al. Polydeoxyribonucleotide (PDRN) promotes human osteoblast proliferation: A new proposal for bone tissue repair. Life Sci. 73, 1973–1983 (2003).
pubmed: 12899922
doi: 10.1016/S0024-3205(03)00547-2
Kim, T. H., Heo, S. Y., Oh, G. W., Heo, S. J. & Jung, W. K. Applications of marine organism-derived polydeoxyribonucleotide: Its Potential in biomedical engineering. Mar. Drugs 19 (2021).