Corticosteroids alter the differentiated phenotype of articular chondrocytes.
Abstract: Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5-3.5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational level by measuring [3H]-proline incorporation into [3H]-hydroxyproline. Fibronectin mRNA splicing patterns were evaluated with ribonuclease protection assays. Cytotoxicity was studied using erythrosin B dye exclusion. Steady-state levels of type II procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentrations were increased from 1 x 10(1) to 1 x 10(8) pg/ml, dropping below 10% of control values by 1 x 10(5) pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 x 10(8) to 1 x 10(9) pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 x 10(4) and 1 x 10(8) pg/ml. Corticosteroid-induced changes in fibronectin isoform levels were evaluated in articular cartilage samples without in vitro culture. The cartilage-specific (V + C)(-) isoform was suppressed in both normal and inflamed joints by a single intraarticular injection (0.1 mg/kg) of methylprednisolone. Combined, these data indicate that methylprednisolone suppresses matrix protein markers of chondrocytic differentiation. Decreased and altered chondrocyte expression of matrix proteins likely contributes to the pathogenesis of corticosteroid-induced cartilage degeneration.
Publication Date: 2001-08-24 PubMed ID: 11518280DOI: 10.1016/S0736-0266(00)00060-7Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research discusses the effect of different concentrations of a drug called methylprednisolone, commonly used as an anti-inflammatory in treatment of joint diseases, on the function and viability of articular chondrocytes or cartilage cells. The study concludes that while low dosages of the drug may protect cartilage, recommended therapeutic doses can potentially suppress or alter the function of these cells and contribute to the degeneration of joint cartilage.
Understanding Articular Chondrocytes and Methylprednisolone
- Articular chondrocytes are cells that are essential for maintaining healthy cartilage, especially in joints.
- Methylprednisolone is a corticosteroid often used as an anti-inflammatory therapy in treating joint diseases, such as arthropathies.
- However, the study points out that even recommended doses of methylprednisolone may damage the articular cartilage, suggesting the drug’s potential harmful effects alongside its beneficial anti-inflammatory properties.
Studying Corticosteroid-induced Changes
- The researchers evaluated how different concentrations of methylprednisolone affect the function and viability of chondrocytes using a variety of methods such as Northern blot analyses, ribonuclease protection assays, and erythrosin B dye exclusion for cytotoxicity.
- With an increase in the concentration of methylprednisolone, there was a decrease in the levels of type II procollagen mRNA, a crucial component for normal cartilage function. This suppression occurred without any concurrent changes in type I procollagen expression.
- The cytotoxic effects were observed at higher concentrations of methylprednisolone.
- Similarly, changes in total collagen (protein) synthesis were less pronounced, but significant suppression occurred between certain concentrations.
Finding and Implications
- The study found that methylprednisolone suppresses matrix protein markers of chondrocytic differentiation, indicating an alteration in cartilage cells’ function.
- The research indicates that the decrease and alteration in chondrocyte expression of matrix proteins may contribute to corticosteroid-induced cartilage degeneration.
- This suggests that while methylprednisolone is effective as an anti-inflammatory, its dose and administration technique should be carefully considered to prevent potential damage to joint cartilage.
Cite This Article
APA
Fubini SL, Todhunter RJ, Burton-Wurster N, Vernier-Singer M, MacLeod JN.
(2001).
Corticosteroids alter the differentiated phenotype of articular chondrocytes.
J Orthop Res, 19(4), 688-695.
https://doi.org/10.1016/S0736-0266(00)00060-7 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / pharmacology
- Cartilage, Articular / cytology
- Cell Differentiation / drug effects
- Cell Survival / drug effects
- Cells, Cultured
- Chondrocytes / cytology
- Chondrocytes / drug effects
- Gene Expression / drug effects
- Horses
- Methylprednisolone Hemisuccinate / pharmacology
- Phenotype
- Procollagen / genetics
- RNA, Messenger / analysis
Grant Funding
- AR44340 / NIAMS NIH HHS
Citations
This article has been cited 17 times.- McMorrow K, Allahabadi S, Frazier L, Quigley R, Serrano B, Cole BJ. One to Two Days of Rest Is Recommended Before Returning to Sport After Intra-Articular Corticosteroid Injection in the High-Level Athlete. Arthrosc Sports Med Rehabil 2023 Oct;5(5):100763.
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