Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro.
Abstract: Osteoarthritis is a frequent sequela of joint disease, especially with severe injuries or if attempts at therapy are unsuccessful. Negative and positive effects of corticosteroid treatment of articular cartilage have been demonstrated by in vitro and in vivo studies. Objective: To assess the metabolic effects of varying dosages of methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) on interleukin-1alpha (IL-1) conditioned equine cartilage explants. Our hypothesis was that lower dosages of corticosteroids would be less detrimental to cartilage metabolism than higher dosages. TA would be less detrimental to cartilage metabolism than MPA. Methods: Treatment groups included articular cartilage explants with no IL-1 (control), IL-1 alone, and IL-1 plus 10, 5, 1 and 0.5 mg/ml MPA or 1.2, 0.6, 0.12 and 0.06 mg/ml TA. Explants were labelled with 35SO4 prior to the beginning and end of the experiment to assess glycosaminoglycan (GAG) degradation and synthesis, respectively. Total GAG content in media and explants and total cartilage DNA were also analysed. Results: MPA and TA reduced GAG synthesis compared to control and IL-1 alone. The highest dosage of MPA (10 mg/ml) reduced GAG synthesis less than lower dosages of MPA and all dosages of TA. Compared to IL-1 alone, all dosages of TA and lower dosages of MPA increased GAG degradation. MPA at 10 mg/ml reduced GAG degradation. Both MPA and TA increased media GAG content compared to control and IL-1 explants. Total cartilage GAGs were unchanged with MPA, but reduced with TA, compared with IL-1 alone. Total cartilage DNA was decreased with MPA and increased with TA compared to IL-1 and control explants. Conclusions: MPA and TA did not counteract the negative effects of IL-1 and did not maintain cartilage metabolism at control levels. Lower dosages of MPA and TA were not less detrimental to cartilage metabolism than higher dosages. TA did not appear to be less harmful than MPA on cartilage metabolism. The results of this study differ from the findings of comparable in vivo studies. Conclusions: The low numbers of horses used in this study limits extrapolation of these findings to the equine population; however, this study also questions the clinical relevance of this in vitro model.
Publication Date: 2003-07-24 PubMed ID: 12875321DOI: 10.2746/042516403775600479Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the effects of different dosages of two corticosteroids, methylprednisolone acetate (MPA) and triamcinolone acetonide (TA), on the metabolic health of equine cartilage conditioned with interleukin-1alpha. Findings indicate that neither MPA nor TA were less harmful at lower dosages, nor did they effectively counteract the negative effects of interleukin-1alpha on cartilage metabolism.
Research Aims and Hypothesis
- The central aim of this research was to evaluate the metabolic effects of varying dosages of methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) on articular cartilage in horses that had been conditioned with interleukin-1alpha (IL-1), a common protein involved in inflammation.
- The study was based on the assumption that lower dosages of corticosteroids would be less harmful to cartilage metabolism than higher dosages and that TA would cause less harm to cartilage metabolism than MPA.
Methods
- Experimentation was conducted on a variety of treatment groups, consisting of articular cartilage explants with no IL-1 (control), IL-1 alone, and IL-1 plus differing quantities of MPA or TA.
- To assess glycosaminoglycan (GAG) degradation and synthesis, which are critical factors in cartilage health, explants were labelled with 35SO4 before and after the testing period.
- Researchers then analyzed total GAG content in the media and explants as well as total cartilage DNA.
Results
- The use of MPA and TA decreased GAG synthesis in comparison to the control group and the group treated with IL-1 alone.
- All dosages of TA and lower dosages of MPA increased GAG degradation. Unexpectedly, a high dosage of MPA (10 mg/ml) reduced GAG degradation.
- Both MPA and TA increased media GAG content when compared to control and IL-1 explants.
- Total cartilage GAGs were found to be reduced with TA and unchanged with MPA when compared with IL-1 alone.
- Impact on total cartilage DNA was found to be mixed, with MPA decreasing and TA increasing levels in comparison to both IL-1 and control explants.
Conclusions
- Both MPA and TA were ineffective at counteracting the negative effects of IL-1 on cartilage metabolism.
- Lower dosages of MPA and TA were not found to be less harmful to cartilage metabolism than higher dosages, opposing the initial hypothesis.
- Additionally, TA did not appear to be less harmful than MPA on cartilage metabolism.
- The results of this in vitro study differed from those of similar in vivo research, most notably concerning the effects of TA dosage on cartilage. The relatively small number of horses used in the study limited the degree to which these findings can be extrapolated to the broader equine population.
Cite This Article
APA
Dechant JE, Baxter GM, Frisbie DD, Trotter GW, McIlwraith CW.
(2003).
Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro.
Equine Vet J, 35(5), 444-450.
https://doi.org/10.2746/042516403775600479 Publication
Researcher Affiliations
- Equine Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / pharmacology
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
- Culture Techniques
- DNA / metabolism
- Dose-Response Relationship, Drug
- Glycosaminoglycans / analysis
- Glycosaminoglycans / metabolism
- Horse Diseases / drug therapy
- Horses
- Interleukin-1 / metabolism
- Male
- Methylprednisolone / analogs & derivatives
- Methylprednisolone / pharmacology
- Methylprednisolone Acetate
- Osteoarthritis / drug therapy
- Osteoarthritis / veterinary
- Triamcinolone Acetonide / pharmacology
Citations
This article has been cited 12 times.- Sullivan SN, Altmann NN, Brokken MT, Durgam SS. In vitro Effects of Methylprednisolone Acetate on Equine Deep Digital Flexor Tendon-Derived Cells. Front Vet Sci 2020;7:486.
- Velloso Alvarez A, Boone LH, Pondugula SR, Caldwell F, Wooldridge AA. Effects of Autologous Conditioned Serum, Autologous Protein Solution, and Triamcinolone on Inflammatory and Catabolic Gene Expression in Equine Cartilage and Synovial Explants Treated With IL-1β in Co-culture. Front Vet Sci 2020;7:323.
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- Byron CR, Trahan RA. Comparison of the Effects of Interleukin-1 on Equine Articular Cartilage Explants and Cocultures of Osteochondral and Synovial Explants. Front Vet Sci 2017;4:152.
- Euppayo T, Punyapornwithaya V, Chomdej S, Ongchai S, Nganvongpanit K. Effects of hyaluronic acid combined with anti-inflammatory drugs compared with hyaluronic acid alone, in clinical trials and experiments in osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord 2017 Sep 6;18(1):387.
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- Diekman BO, Estes BT, Guilak F. The effects of BMP6 overexpression on adipose stem cell chondrogenesis: Interactions with dexamethasone and exogenous growth factors. J Biomed Mater Res A 2010 Jun 1;93(3):994-1003.
- Fischer J, Pasztorek M, Gossy N, Otahal A, De Luna A, Nehrer S, Rosser J. Stem cell modelling of osteoarthritis using an organ-on-a-chip approach. Inflamm Regen 2025 Oct 28;45(1):32.
- Guidoni K, Chiaradia E, Pepe M, Di Meo A, Tognoloni A, Seccaroni M, Beccati F. The Combined Use of Triamcinolone and Platelet-Rich Plasma in Equine Metacarpophalangeal Joint Osteoarthritis Treatments: An In Vivo and In Vitro Study. Animals (Basel) 2024 Dec 17;14(24).
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