nach oben

Inflammation Research

Erschienen in:

29.01.2021 | Review

Tetracycline use in treating osteoarthritis: a systematic review

verfasst von: Brooks N. Platt, Cale A. Jacobs, Caitlin E. W. Conley, Austin V. Stone

Erschienen in: Inflammation Research | Ausgabe 3/2021

Einloggen, um Zugang zu erhalten

Abstract

Background and aims

The purpose of the review was to synthesize the current literature regarding tetracyclines in the treatment of osteoarthritis.

Methods

Using multiple databases, a systematic review was performed with customized search terms crafted to identify studies examining doxycycline or minocycline in the treatment of osteoarthritis. Results were classified into basic science mechanistic studies, in vivo animal studies, and human clinical trials. A total of 1446 potentially relevant studies were reviewed, and after exclusion criteria were applied, 23 investigations were included in the final analysis.

Results

From 12 basic science mechanistic studies, we report on three main mechanisms by which tetracyclines may exert benefit in osteoarthritis progression: matrix metalloproteinase inhibition, immunomodulation, and nitric oxide synthase inhibition. Seven animal studies showed generally encouraging results. Four articles reported human clinical studies, showing mixed results in the treatment of osteoarthritis, potentially related to the choice of patient population, primary outcomes, and timing of treatment.

Conclusion

Tetracyclines have the potential to benefit osteoarthritis patients via multiple mechanisms. Further study is warranted to examine the optimal dose and timing of tetracycline treatment in osteoarthritis.

Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartil. 2013;21:16–21.CrossRef

Woodell-May JE, Sommerfeld SD. Role of inflammation and the immune system in the progression of osteoarthritis. J Orthop Res. 2020;38:253–7.PubMedCrossRef

Kraus LF, Scheurmann N, Frenzel DF, Tasdogan A, Weiss JM. 9-cis-Retinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed-type allergy. Contact Dermatitis. 2018;78:41–54.PubMedCrossRef

Haraden CA, Huebner JL, Hsueh MF, Li YJ, Kraus VB. Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation. Arthritis Res Ther. 2019;21:146.PubMedPubMedCentralCrossRef

Daghestani HN, Pieper CF, Kraus VB. Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis. Arthritis Rheumatol. 2015;67:956–65.PubMedPubMedCentralCrossRef

Liu-Bryan R, Terkeltaub R. Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous Toll-like receptor 2/Toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice. Arthritis Rheum. 2010;62:2004–12.PubMedPubMedCentral

Yammani RR, Carlson CS, Bresnick AR, Loeser RF. Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: role of the receptor for advanced glycation end products. Arthritis Rheum. 2006;54:2901–11.PubMedCrossRef

Zreiqat H, Belluoccio D, Smith MM, Wilson R, Rowley LA, Jones K, et al. S100A8 and S100A9 in experimental osteoarthritis. Arthritis Res Ther. 2010;12:R16.PubMedPubMedCentralCrossRef

Huang ZY, Perry E, Huebner JL, Katz B, Li YJ, Kraus VB. Biomarkers of inflammation - LBP and TLR- predict progression of knee osteoarthritis in the DOXY clinical trial. Osteoarthritis Cartil. 2018;26:1658–65.CrossRef

10.

Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta. 2012;1824:133–45.PubMedCrossRef

11.

Xu L, Servais J, Polur I, Kim D, Lee PL, Chung K, et al. Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice. Arthritis Rheum. 2010;62:2736–44.PubMedPubMedCentralCrossRef

12.

Chinzei N, Brophy RH, Duan X, Cai L, Nunley RM, Sandell LJ, et al. Molecular influence of anterior cruciate ligament tear remnants on chondrocytes: a biologic connection between injury and osteoarthritis. Osteoarthritis Cartil. 2018;26:588–99.CrossRef

13.

Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64:1697–707.PubMedPubMedCentralCrossRef

14.

Fields GB. The rebirth of matrix metalloproteinase inhibitors: moving beyond the dogma. Cells. 2019; 8.

15.

Nelson ML, Levy SB. The history of the tetracyclines. Ann N Y Acad Sci. 2011;1241:17–32.PubMedCrossRef

16.

Zhou YQ, Liu DQ, Chen SP, Sun J, Wang XM, Tian YK, et al. Minocycline as a promising therapeutic strategy for chronic pain. Pharmacol Res. 2018;134:305–10.PubMedCrossRef

17.

da Costa BR, Nuesch E, Reichenbach S, Juni P, Rutjes AW. Doxycycline for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 2012; 11:CD007323.

18.

Greenwald RA. The road forward: the scientific basis for tetracycline treatment of arthritic disorders. Pharmacol Res. 2011;64:610–3.PubMedCrossRef

19.

Greenwald RA, Golub LM, Lavietes B, Ramamurthy NS, Gruber B, Laskin RS, et al. Tetracyclines inhibit human synovial collagenase in vivo and in vitro. J Rheumatol. 1987;14:28–32.PubMed

20.

Yu LP Jr, Smith GN Jr, Hasty KA, Brandt KD. Doxycycline inhibits type XI collagenolytic activity of extracts from human osteoarthritic cartilage and of gelatinase. J Rheumatol. 1991;18:1450–2.PubMed

21.

Smith GN Jr, Yu LP Jr, Brandt KD, Capello WN. Oral administration of doxycycline reduces collagenase and gelatinase activities in extracts of human osteoarthritic cartilage. J Rheumatol. 1998;25:532–5.PubMed

22.

Smith GN Jr, Mickler EA, Hasty KA, Brandt KD. Specificity of inhibition of matrix metalloproteinase activity by doxycycline: relationship to structure of the enzyme. Arthritis Rheum. 1999;42:1140–6.PubMedCrossRef

23.

Shlopov BV, Smith GN Jr, Cole AA, Hasty KA. Differential patterns of response to doxycycline and transforming growth factor beta1 in the down-regulation of collagenases in osteoarthritic and normal human chondrocytes. Arthritis Rheum. 1999;42:719–27.PubMedCrossRef

24.

Shlopov BV, Stuart JM, Gumanovskaya ML, Hasty KA. Regulation of cartilage collagenase by doxycycline. J Rheumatol. 2001;28:835–42.PubMed

25.

Vandooren J, Knoops S, Aldinucci Buzzo JL, Boon L, Martens E, Opdenakker G, et al. Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: a comparative study. PLoS ONE. 2017;12:e0174853.PubMedPubMedCentralCrossRef

26.

Kloppenburg M, Breedveld FC, Miltenburg AM, Dijkmans BA. Antibiotics as disease modifiers in arthritis. Clin Exp Rheumatol. 1993;11(Suppl 8):S113–5.PubMed

27.

Kloppenburg M, Brinkman BM, de Rooij-Dijk HH, Miltenburg AM, Daha MR, Breedveld FC, et al. The tetracycline derivative minocycline differentially affects cytokine production by monocytes and T lymphocytes. Antimicrob Agents Chemother. 1996;40:934–40.PubMedPubMedCentralCrossRef

28.

Amin AR, Attur MG, Thakker GD, Patel PD, Vyas PR, Patel RN, et al. A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci U S A. 1996;93:14014–9.PubMedPubMedCentralCrossRef

29.

Borderie D, Hernvann A, Hilliquin P, Lemarchal H, Kahan A, Ekindjian OG. Tetracyclines inhibit nitrosothiol production by cytokine-stimulated osteoarthritic synovial cells. Inflamm Res. 2001;50:409–14.PubMedCrossRef

30.

Steinmeyer J, Kordelle J, Sturz H. In vitro inhibition of aggrecanase activity by tetracyclines and proteoglycan loss from osteoarthritic human articular cartilage. J Orthop Res. 2010;28:828–33.PubMedCrossRef

31.

Lee HH, O’Malley MJ, Friel NA, Chu CR. Effects of doxycycline on mesenchymal stem cell chondrogenesis and cartilage repair. Osteoarthritis Cartil. 2013;21:385–93.CrossRef

32.

Lu HT, Sheu MT, Lin YF, Lan J, Chin YP, Hsieh MS, et al. Injectable hyaluronic-acid-doxycycline hydrogel therapy in experimental rabbit osteoarthritis. BMC Vet Res. 2013;9:68.PubMedPubMedCentralCrossRef

33.

Aydin O, Korkusuz F, Korkusuz P, Tezcaner A, Bilgic E, Yaprakci V, et al. In vitro and in vivo evaluation of doxycycline-chondroitin sulfate/PCLmicrospheres for intraarticular treatment of osteoarthritis. J Biomed Mater Res B Appl Biomater. 2015;103:1238–48.PubMedCrossRef

34.

Yu LP Jr, Smith GN Jr, Brandt KD, Myers SL, O’Connor BL, Brandt DA. Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis Rheum. 1992;35:1150–9.PubMedCrossRef

35.

Pardy CK, Matyas JR, Zernicke RF. Doxycycline effects on mechanical and morphometrical properties of early- and late-stage osteoarthritic bone following anterior cruciate ligament injury. J Appl Physiol. 1985;2004(97):1254–60.

36.

Dinc M, Bilgen MS, Kucukalp A, Bilgen OF. An assessment of the chondroprotective effects of intra-articular application of statin and tetracycline on early-stage experimental osteoarthritis. ISRN Orthop. 2012;2012:182097.PubMedPubMedCentralCrossRef

37.

Pinney JR, Taylor C, Doan R, Burghardt AJ, Li X, Kim HT, et al. Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis. Magn Reson Imaging. 2012;30:271–82.PubMedCrossRef

38.

Israel HA, Ramamurthy NS, Greenwald R, Golub L. The potential role of doxycycline in the treatment of osteoarthritis of the temporomandibular joint. Adv Dent Res. 1998;12:51–5.PubMedCrossRef

39.

Brandt KD, Mazzuca SA, Katz BP, Lane KA, Buckwalter KA, Yocum DE, et al. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. 2005;52:2015–25.PubMedCrossRef

40.

Snijders GF, van den Ende CH, van Riel PL, van den Hoogen FH, den Broeder AA, group Ns. The effects of doxycycline on reducing symptoms in knee osteoarthritis: results from a triple-blinded randomised controlled trial. Ann Rheum Dis 2011; 70:1191–6.

41.

Ma J, Talukdar R, Gainers-Hasugluw V. Pilot open observations on doxycycline treatment for erosive osteoarthritis of the hand. J Clin Rheumatol. 2015;21:38–9.PubMedCrossRef

42.

Tilley BC, Alarcon GS, Heyse SP, Trentham DE, Neuner R, Kaplan DA, et al. Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Ann Intern Med. 1995;122:81–9.PubMedCrossRef

43.

O’Dell JR, Haire CE, Palmer W, Drymalski W, Wees S, Blakely K, et al. Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 1997;40:842–8.PubMedCrossRef

44.

O’Dell JR, Paulsen G, Haire CE, Blakely K, Palmer W, Wees S, et al. Treatment of early seropositive rheumatoid arthritis with minocycline: four-year followup of a double-blind, placebo-controlled trial. Arthritis Rheum. 1999;42:1691–5.PubMedCrossRef

45.

O’Dell JR, Blakely KW, Mallek JA, Eckhoff PJ, Leff RD, Wees SJ, et al. Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum. 2001;44:2235–41.PubMedCrossRef

46.

Stone M, Fortin PR, Pacheco-Tena C, Inman RD. Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstrates clinical benefit with reduction in disease activity. J Rheumatol. 2003;30:2112–22.PubMed

47.

Thomas AC, Hubbard-Turner T, Wikstrom EA, Palmieri-Smith RM. Epidemiology of posttraumatic osteoarthritis. J Athl Train. 2017;52:491–6.PubMedPubMedCentralCrossRef

48.

Englund M, Guermazi A, Gale D, Hunter DJ, Aliabadi P, Clancy M, et al. Incidental meniscal findings on knee MRI in middle-aged and elderly persons. N Engl J Med. 2008;359:1108–15.PubMedPubMedCentralCrossRef

49.

Jacobs CA, Hunt ER, Conley CE, Johnson DL, Stone AV, Huebner JL, et al. Dysregulated inflammatory response related to cartilage degradation after ACL injury. Med Sci Sports Exerc. 2020;52:535–41.PubMedCrossRef

50.

Stone AV, Loeser RF, Vanderman KS, Long DL, Clark SC, Ferguson CM. Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis. Osteoarthritis Cartil. 2014;22:264–74.CrossRef

51.

Lohmander LS, Atley LM, Pietka TA, Eyre DR. The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis. Arthritis Rheum. 2003;48:3130–9.PubMedCrossRef

52.

Brandt KD. Why should we expect a structure-modifying osteoarthritis drug to relieve osteoarthritis pain? Ann Rheum Dis. 2011;70:1175–7.PubMedCrossRef

53.

Neogi T, Bowes MA, Niu J, De Souza KM, Vincent GR, Goggins J, et al. Magnetic resonance imaging-based three-dimensional bone shape of the knee predicts onset of knee osteoarthritis: data from the osteoarthritis initiative. Arthritis Rheum. 2013;65:2048–58.PubMedPubMedCentralCrossRef

54.

Chu CR, Williams AA, Coyle CH, Bowers ME. Early diagnosis to enable early treatment of pre-osteoarthritis. Arthritis Res Ther. 2012;14:212.PubMedPubMedCentralCrossRef

55.

Potter HG, Koff MF. MR imaging tools to assess cartilage and joint structures. HSS J. 2012;8:29–32.PubMedPubMedCentralCrossRef

56.

Shultz RB, Zhong Y. Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury. Neural Regen Res. 2017;12:702–13.PubMedPubMedCentralCrossRef

57.

Sagar DR, Burston JJ, Hathway GJ, Woodhams SG, Pearson RG, Bennett AJ, et al. The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain. Mol Pain. 2011;7:88.PubMedPubMedCentralCrossRef

58.

Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013;11:200.PubMedPubMedCentralCrossRef

59.

Dean OM, Data-Franco J, Giorlando F, Berk M. Minocycline: therapeutic potential in psychiatry. CNS Drugs. 2012;26:391–401.PubMedCrossRef

60.

Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, et al. Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: a positron emission tomography study. Biol Psychiatry. 2018;83:61–9.PubMedCrossRef

61.

Cai DB, Zheng W, Zhang QE, Ng CH, Ungvari GS, Huang X, et al. Minocycline for depressive symptoms: a meta-analysis of randomized, double-blinded, placebo-controlled trials. Psychiatr Q. 2020.

62.

Schmidtner AK, Slattery DA, Glasner J, Hiergeist A, Gryksa K, Malik VA, et al. Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner. Transl Psychiatry. 2019;9:223.PubMedPubMedCentralCrossRef

63.

Cerisano G, Buonamici P, Valenti R, Sciagra R, Raspanti S, Santini A, et al. Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodelling: the TIPTOP trial. Eur Heart J. 2014;35:184–91.PubMedCrossRef

64.

Bench TJ, Jeremias A, Brown DL. Matrix metalloproteinase inhibition with tetracyclines for the treatment of coronary artery disease. Pharmacol Res. 2011;64:561–6.PubMedCrossRef

65.

Jung JY, Ahn Y, Khare S, Gokulan K, Pineiro SA, Cerniglia CE. An in vitro study to assess the impact of tetracycline on the human intestinal microbiome. Anaerobe. 2018;49:85–94.PubMedCrossRef

66.

Keerthisinghe TP, Wang M, Zhang Y, Dong W, Fang M. Low-dose tetracycline exposure alters gut bacterial metabolism and host-immune response: “personalized” effect? Environ Int. 2019;131:104989.PubMedCrossRef

67.

Gossage DL, Cieslarova B, Ap S, Zheng H, Xin Y, Lal P, et al. Phase 1b study of the safety, pharmacokinetics, and disease-related outcomes of the matrix metalloproteinase-9 inhibitor andecaliximab in patients with rheumatoid arthritis. Clin Ther. 2018;40(156–165):e5.

Titel: Tetracycline use in treating osteoarthritis: a systematic review
verfasst von: Brooks N. Platt
Cale A. Jacobs
Caitlin E. W. Conley
Austin V. Stone
Publikationsdatum: 29.01.2021
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 3/2021
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-021-01435-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Intervallfasten zur Regeneration des Herzmuskels?

14.05.2024 Herzinfarkt Nachrichten

Die Nahrungsaufnahme auf wenige Stunden am Tag zu beschränken, hat möglicherweise einen günstigen Einfluss auf die Prognose nach akutem ST-Hebungsinfarkt. Darauf deutet eine Studie an der Uniklinik in Halle an der Saale hin.

Klimaschutz beginnt bei der Wahl des Inhalators

14.05.2024 Klimawandel Podcast

Auch kleine Entscheidungen im Alltag einer Praxis können einen großen Beitrag zum Klimaschutz leisten. Die neue Leitlinie zur "klimabewussten Verordnung von Inhalativa" geht mit gutem Beispiel voran, denn der Wechsel vom klimaschädlichen Dosieraerosol zum Pulverinhalator spart viele Tonnen CO₂. Leitlinienautor PD Dr. Guido Schmiemann erklärt, warum nicht nur die Umwelt, sondern auch Patientinnen und Patienten davon profitieren.

Typ-2-Diabetes und Depression folgen oft aufeinander

14.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes sind überdurchschnittlich gefährdet, in den nächsten Jahren auch noch eine Depression zu entwickeln – und umgekehrt. Besonders ausgeprägt ist die Wechselbeziehung laut GKV-Daten bei jüngeren Erwachsenen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Background and aims

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2021

Therapeutic treatment of dietary docosahexaenoic acid for particle-induced pulmonary inflammation in Balb/c mice

microRNA-155-3p attenuates intervertebral disc degeneration via inhibition of KDM3A and HIF1α

Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by altering macrophage polarization via the miR-449a/NLRP3 axis

Regulation of Toll-like receptor-mediated inflammatory response by microRNA-152-3p-mediated demethylation of MyD88 in systemic lupus erythematosus

Notch signaling pathway in infectious diseases: role in the regulation of immune response