Skip to main content
SpringerLink
Log in

Resveratrol-silica aerogel nanodrug complex system enhances the treatment of sports osteoarthritis by activating SIRT-1

  • Research
  • Published:
Advanced Composites and Hybrid Materials Aims and scope Submit manuscript

Abstract

Sports osteoarthritis (OA) is the most prevalent chronic joint disease in professional and recreational athletes. Resveratrol (RES), which is extracted from plants, has excellent anti-inflammatory properties. However, its application in OA treatment is limited by its poor water solubility, low bioavailability, and rapid metabolism. In this study, a silica aerogel (SA) was prepared through the sol–gel method and used to carry RES in the form of a nanodrug complex system (RSA) with a high drug–loading rate of 21.8% and a sustained release effect that lasted more than 6 hours. RSA had good biocompatibility in human chondrocytes when the concentration was less than 40 μg/mL and enhanced the anti-inflammatory actions of RES in vitro. A rat model of exercise-induced osteoarthritis was constructed to examine the therapeutic effects of RSA in vivo. Furthermore, the inflammatory factors involved in cartilage degradation and catabolism were reduced to 14.6–19.1% those of the original values after RES intervention, while the expression of type II collagen significantly increased. Moreover, RES was found to activate SIRT-1 by inhibiting the NF-κB-mediated inflammatory pathway, which also alleviated the degradation of cartilage matrix. These results indicated that the use of RSA could provide a novel noninvasive approach for targeted OA therapy with the potential for oral drug delivery.

Graphical abstract

A resveratrol-silica aerogel (RSA) nanodrug complex system with a high drug–loading rate and a sustained release effect efficiently enhance the treatment of sports osteoarthritis by activating SIRT-1 through oral administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Some or all data or models used during the study are available from the corresponding author by request.

References

  1. Litwic A, Edwards MH, Dennison EM, Cooper C (2013) Epidemiology and burden of osteoarthritis. Br Med Bull 105(1):185–199. https://doi.org/10.1093/bmb/lds038

    Article  Google Scholar 

  2. Malfait AM (2016) Osteoarthritis year in review 2015: biology. Osteoarthritis Cartilage 24(1):21–26. https://doi.org/10.1016/j.joca.2015.09.010

    Article  CAS  Google Scholar 

  3. Wang KZ, Lei GH, Hu YC (2021) Chinese guideline for diagnosis and treatment of osteoarthritis. Chinese J Orthop 41(18):1291–1314. https://doi.org/10.3760/cma.j.cn121113-20210624-00424

    Article  Google Scholar 

  4. Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE (2019) OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil 27(11):1578–1589. https://doi.org/10.1016/j.joca.2019.06.011

    Article  CAS  Google Scholar 

  5. Persson MSM, Stocks J, Varadi G, Hashempur MH, Van Middelkoop M, Bierma-Zeinstra S, Walsh DA, Doherty M, Zhang W (2020) Predicting response to topical non-steroidal anti-inflammatory drugs in osteoarthritis: an individual patient data meta-analysis of randomized controlled trials. Rheumatol 59(9):2207–2216. https://doi.org/10.1093/rheumatology/keaa113

    Article  Google Scholar 

  6. Lee AS, Ellman MB, Yan D, Kroin JS, Cole BJ, van Wijnen AJ, Im HJ (2013) A current review of molecular mechanisms regarding osteoarthritis and pain. Gene 527(2):440–447. https://doi.org/10.1016/j.gene.2013.05.069

    Article  CAS  Google Scholar 

  7. Kang DG, Lee HJ, Lee CJ, Park JS (2018) Inhibition of the expression of matrix metalloproteinases in articular chondrocytes by resveratrol through affecting nuclear factor-kappa b signaling pathway. Biomol Ther 26(6):560–567. https://doi.org/10.4062/biomolther.2018.132

    Article  CAS  Google Scholar 

  8. Collins JA, Moots RJ, Clegg PD, Milner PI (2015) Resveratrol and N-acetylcysteine influence redox balance in equine articular chondrocytes under acidic and very low oxygen conditions. Free Radic Biol Med 86:57–64. https://doi.org/10.1016/j.freeradbiomed.2015.05.008

    Article  CAS  Google Scholar 

  9. Wenzel E, Somoza V (2005) Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res 49(5):472–481. https://doi.org/10.1002/mnfr.200500010

    Article  CAS  Google Scholar 

  10. Montsko G, Nikfardjam MSP, Szabo Z, Boddi K, Lorand T, Ohmacht R, Mark L (2008) Determination of products derived from trans-resveratrol UV photoisomerisation by means of HPLC-APCI-MS. J Photochem Photobiol A Chem 196(1):44–50. https://doi.org/10.1016/j.jphotochem.2007.11.011

    Article  CAS  Google Scholar 

  11. Wang W, Sun L, Zhang P, Song J, Liu W (2014) An anti-inflammatory cell-free collagen/resveratrol scaffold for repairing osteochondral defects in rabbits. Acta Biomater 10(12):4983–4995. https://doi.org/10.1016/j.actbio.2014.08.022

    Article  CAS  Google Scholar 

  12. Choi SM, Lee KM, Ryu SB, Park YJ, Hwang YG, BaekD CY, Park KH, Park KD, Lee JW (2018) Enhanced articular cartilage regeneration with SIRT1-activated MSCs using gelatin-based hydrogel. Cell Death Dis 9(9):886. https://doi.org/10.1038/s41419-018-0914-1

    Article  CAS  Google Scholar 

  13. Sheu SY, Chen WS, Sun JS, Lin FH, Wu T (2013) Biological characterization of oxidized hyaluronic acid/resveratrol hydrogel for cartilage tissue engineering. J Biomed Mater Res - Part A 101(12):3457–3466. https://doi.org/10.1002/jbm.a.34653

    Article  CAS  Google Scholar 

  14. Wu G, Wang L, Li H, Ke Y, Yao Y (2016) Function of sustained released resveratrol on IL-1β-induced hBMSC MMP13 secretion inhibition and chondrogenic differentiation promotion. J Biomater Appl 30(7):930–939. https://doi.org/10.1177/0885328215614425

    Article  CAS  Google Scholar 

  15. Kann B, Spengler C, Coradini K, Rigo LA, Bennink ML, Jacobs K, Offerhaus HL, Beck RCR, Windbergs M (2016) Intracellular delivery of poorly soluble polyphenols: elucidating the interplay of self-assembling nanocarriers and human chondrocytes. Anal Chem 88(14):7014–7022. https://doi.org/10.1021/acs.analchem.6b00199

    Article  CAS  Google Scholar 

  16. Le Clanche S, Cheminel T, Rannou F, Bonnefont-Rousselot D, Borderie D, Charrueau C (2018) Use of resveratrol self-emulsifying systems in T/C28a2 cell line as beneficial effectors in cellular uptake and protection against oxidative stress-mediated death. Front Pharmacol. https://doi.org/10.3389/fphar.2018.00538

    Article  Google Scholar 

  17. Wang J, Wang HY, Zhu RR, Liu Q, Fei J, Wang SL (2015) Anti-inflammatory activity of curcumin-loaded solid lipid nanoparticles in IL-1β transgenic mice subjected to the lipopolysaccharide-induced sepsis. Biomaterials 53:475–483. https://doi.org/10.1016/j.biomaterials.2015.02.116

    Article  CAS  Google Scholar 

  18. Yang L, He XL, Jing GX, Wang H, Niu JH, Qian YC, Wang SL (2021) Layered double hydroxide nanoparticles with osteogenic effects as miRNA carriers to synergistically promote osteogenesis of MSCs. ACS Appl Mater Interfaces 13(41):48386–48402. https://doi.org/10.1021/acsami.1c14382

    Article  CAS  Google Scholar 

  19. Zhu RR, Zhu XF, Zhu YJ, Wang ZJ, He XL, Wu ZR, Xue L, Fan WY, Huang RQ, Xu Z, Qi X, Xu W, Yu Y, Ren YL, Li C, Cheng Q, Ling L, Wang SL, Cheng LM (2021) Immunomodulatory layered double hydroxide nanoparticles enable neurogenesis by targeting transforming growth factor-β receptor 2. ACS Nano 15(2):2812–2830. https://doi.org/10.1021/acsnano.0c08727

    Article  CAS  Google Scholar 

  20. Ji XJ, Zhong Y, Li CY, Chu JJ, Wang HQ, Xing Z, Niu TT, Zhang ZH, Du A (2021) Nanoporous carbon aerogels for laser-printed wearable sensors. ACS Appl Nano Mater 4(7):6796–6804. https://doi.org/10.1021/acsanm.1c00858

    Article  CAS  Google Scholar 

  21. Ji XJ, Wang HQ, Chen TZ, Zhang T, Chu JJ, Du A (2020) Intrinsic negative TCR of superblack carbon aerogel films and their ultrabroad band response from UV to microwave. Carbon 161:590–598. https://doi.org/10.1016/j.carbon.2020.01.101

    Article  CAS  Google Scholar 

  22. Yang JM, Cui NX, Han DX, Shen J, Wu GM, Zhang ZH, Qin LL, Zhou B, Du A (2021) A simple strategy for constructing hierarchical composite electrodes of PPy-posttreated 3D-printed carbon aerogel with ultrahigh areal capacitance over 8000 mF cm-2. Adv Mater Technol 2101325. https://doi.org/10.1002/admt.202101325

  23. Riley L, Schirmer L, Segura T (2019) Granular hydrogels: emergent properties of jammed hydrogel microparticles and their applications in tissue repair and regeneration. Curr Opin Biotechnol 60:1–8. https://doi.org/10.1016/j.copbio.2018.11.001

    Article  CAS  Google Scholar 

  24. Xie PT, Sun W, Du A, Hou Q, Wu GM, Fan RH (2021) Epsilon-negative carbon aerogels with state transition from dielectric to degenerate semiconductor. Adv Electron Mater 7(3). https://doi.org/10.1002/aelm.202000877

  25. Sun W, Du A, Feng Y, Shen J, Huang SM, Tang J, Zhou B (2016) Super black material from low-density carbon aerogels with subwavelength structures. ACS Nano 10(10):9123–9128. https://doi.org/10.1021/acsnano.6b02039

    Article  CAS  Google Scholar 

  26. Xie PT, Sun W, Liu Y, Du A, Zhang ZD, Wu GM, Fan RH (2018) Carbon aerogels towards new candidates for double negative metamaterials of low density. Carbon 129:598–606. https://doi.org/10.1016/j.carbon.2017.12.009

    Article  CAS  Google Scholar 

  27. Wu S, Du A, Huang SM, Sun W, Zu GQ, Xiang YL, Li CH, Zhou B (2016) Effects of monomer rigidity on the microstructures and properties of polyimide aerogels cross-linked with low cost aminosilane. RSC Adv 6(27):22868–22877. https://doi.org/10.1039/C5RA28152K

    Article  CAS  Google Scholar 

  28. Du A, Zhou B, Zhang ZH, Shen J (2013) A special material or a new state of matter: a review and reconsideration of the aerogel. Materials 6(3):941–968. https://doi.org/10.3390/ma6030941

    Article  CAS  Google Scholar 

  29. Stergar J, Maver U (2016) Review of aerogel-based materials in biomedical applications. J Sol-Gel Sci Technol 77(3):738–752. https://doi.org/10.1007/s10971-016-3968-5

    Article  CAS  Google Scholar 

  30. Liu MF, Du A, Li TM, Zhang T, Zhang ZH, Cao GW, Li HW, Shen J, Zhou B (2019) Simple deceleration mechanism confirmed in the terminal hypervelocity impacted tracks in SiO2 aerogel. Icarus 317:365–372. https://doi.org/10.1016/j.icarus.2018.08.017

    Article  CAS  Google Scholar 

  31. Du A, Ma Y, Liu MF, Zhang ZH, Cao GW, Li HW, Wang L, Si PJ, Shen J, Zhou B (2021) Morphology analysis of tracks in the aerogels impacted by hypervelocity irregular particles. High Power Laser Sci and Eng 9(2):e14. https://doi.org/10.1017/hpl.2020.54

    Article  CAS  Google Scholar 

  32. Alemán J, Chadwick AV, He J, Hess M, Horie K, Jones RG, Kratochvíl P, Meisel I, Mita I, Moad G, Penczek S, Stepto RFT (2007) Definitions of terms relating to the structure and processing of sols, gels, networks, and inorganic-organic hybrid materials (IUPAC Recommendations 2007). Pure Appl Chem 79(10):1801–1827. https://doi.org/10.1351/pac200779101801

    Article  CAS  Google Scholar 

  33. Juère E, Florek J, Bouchoucha M, Jambhrunkar S, Wong KY, Popat A, Kleitz F (2017) In vitro dissolution, cellular membrane permeability, and anti-inflammatory response of resveratrol-encapsulated mesoporous silica nanoparticles. Mol Pharm 14(12):4431–4441. https://doi.org/10.1021/acs.molpharmaceut.7b00529

    Article  CAS  Google Scholar 

  34. Summerlin N, Qu Z, Pujara N, Sheng Y, Jambhrunkar S, McGuckin M, Popat A (2016) Colloidal mesoporous silica nanoparticles enhance the biological activity of resveratrol. Colloid Surf B-Biointerfaces 144:1–7. https://doi.org/10.1016/j.colsurfb.2016.03.076

    Article  CAS  Google Scholar 

  35. Qin LL, He YW, Zhao XY, Zhang T, Qin Y, Du A (2020) Preparation, characterization, and in vitro sustained release profile of resveratrol-loaded silica aerogel. Molecules 25(12):2752. https://doi.org/10.3390/molecules25122752

    Article  CAS  Google Scholar 

  36. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H (2011) Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7(1):33–42. https://doi.org/10.1038/nrrheum.2010.196

    Article  CAS  Google Scholar 

  37. Alaaeddine N, DiBattista JA, Pelletier JP, Cloutier JM, Kiansa K, Dupuis M, Martel-Pelletier J (1997) Osteoarthritic synovial fibroblasts possess an increased level of tumor necrosis factor-receptor 55 (TNF-R55) that mediates biological activation by TNF-alpha. J Rheumatol 24(10):1985–1994

    CAS  Google Scholar 

  38. Naume B, Shalaby R, Lesslauer W, Espevik T (1991) Involvement of the 55- and 75-kDa tumor necrosis factor receptors in the generation of lymphokine-activated killer cell activity and proliferation of natural killer cells. J Immunol 146(9):3045–3048

    Article  CAS  Google Scholar 

  39. Guerne PA, Carson DA, Lotz M (1990) IL-6 production by human articular chondrocytes-modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J Immunol 144(2):499–505

    Article  CAS  Google Scholar 

  40. Bender S, Haubeck HD, Van de Leur E, Dufhues G, Schiel X, Lauwerijns J, Greiling H, Heinrich PC (1990) Interleukin-1β induces synthesis and secretion of interleukin-6 in human chondrocytes. FEBS Lett 263(2):321–324. https://doi.org/10.1016/0014-5793(90)81404-C

    Article  CAS  Google Scholar 

  41. Setton LA, Elliott DM, Mow VC (1999) Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage 7(1):2–14. https://doi.org/10.1053/joca.1998.0170

    Article  CAS  Google Scholar 

  42. Mäkelä JTA, Han SK, Herzog W, Korhonen RK (2015) Very early osteoarthritis changes sensitively fluid flow properties of articular cartilage. J Biomech 48(12):3369–3376. https://doi.org/10.1016/j.jbiomech.2015.06.010

    Article  Google Scholar 

  43. Li YS, Xiao WF, Wu P, Deng ZH, Zeng C, Li H, Yang TH, Lei G (2016) The expression of SIRT1 in articular cartilage of patients with knee osteoarthritis and its correlat. J Orthop Surg Res 11(1):144. https://doi.org/10.1186/s13018-016-0477-8

    Article  Google Scholar 

  44. Yamamoto T, Miyaji N, Kataoka K, Nishida K, Nagai K, Kanzaki N, HoshinoY KR, Matsushita T (2021) Knee osteoarthritis progression is delayed in silent information regulator 2 ortholog 1 knock-in Mice. Int J Mol Sci 22(19):10689. https://doi.org/10.3390/ijms221910685

    Article  CAS  Google Scholar 

  45. Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A (2013) Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cel Signal 25(10):1939–1948. https://doi.org/10.1016/j.cellsig.2013.06.007

    Article  CAS  Google Scholar 

  46. Van den Berg WB (2011) Osteoarthritis year 2010 in review: pathomechanisms. Osteoarthr Cartil 19(4):338–341. https://doi.org/10.1016/j.joca.2011.01.022

    Article  Google Scholar 

  47. Matsushita T, Sasaki H, Takayama K, Ishida K, Matsumoto T, Kubo S, Matsuzaki T, Nishida K, Kurosaka M, Kuroda R (2013) The overexpression of SIRT1 inhibited osteoarthritic gene expression changes induced by interleukin-1β in human chondrocytes. J Orthop Res 31(4):531–537. https://doi.org/10.1002/jor.22268

    Article  CAS  Google Scholar 

Download references

Funding

This work was funded by the National Key Research and Development Program of China (2017YFA0204600), the National Natural Science Foundation of China (Grant No. 31771313), and the China Postdoctoral Science Foundation (2021M692442).

Author information

Author notes

  1. Lili Qin and Guoxin Jing contributed equally to this article.

Authors and Affiliations

  1. Department of Physical Education, Sports and Health Research Center, Tongji University, Shanghai, 200092, People’s Republic of China

    Lili Qin, Ningxin Cui, Zhen Xu, Yiwei He, Yao Qin, Tianfeng Lu & Jingyu Sun

  2. Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200092, People’s Republic of China

    Guoxin Jing & Shilong Wang

  3. Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, People’s Republic of China

    Ai Du

Authors
  1. Lili Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guoxin Jing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ningxin Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yiwei He
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yao Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tianfeng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jingyu Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ai Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shilong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

L.Q., A.D, and S.W. provided the conception and design of the study. L.Q., N.C., and Y.H. completed the material synthesis and animal experiments. L.Q. and G.J. completed the in vitro experiments. L.Q., A.D., G.J., and N.C. co-wrote the main manuscript text. Z.X., Y.Q., T.L., and J.S. performed image and data analyses. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Ai Du or Shilong Wang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 677 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qin, L., Jing, G., Cui, N. et al. Resveratrol-silica aerogel nanodrug complex system enhances the treatment of sports osteoarthritis by activating SIRT-1. Adv Compos Hybrid Mater 6, 3 (2023). https://doi.org/10.1007/s42114-022-00576-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s42114-022-00576-2

Keywords

Search

Navigation