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 I1 procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentrations were increased from 1 x lo1 to 1 x 10' pg/ml, dropping below 10% of control values by 1 Y lo5 pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 x loR to 1 A lo9 pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 x lo4 and 1 x lo8 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.

Increased Chondrocyte Death after Steroid and Local Anesthetic Combination

“…Intraarticular injection of corticosteroid is an effective and common treatment for osteoarthritis, although clinical evidence suggests it provides a relatively short-lived benefit in pain relief [16,21,26,27,37,42,44,47]. One study suggested certain dosages of corticosteroids used clinically as antiinflammatory drugs for osteoarthritis are harmful to articular cartilage [15], whereas lower dosages are reportedly chondroprotective and delay progression of cartilage lesions [8,28,36,38,43]. In vitro we found betamethasone and prednisolone had no effect in inducing chondrocyte cell death when compared with the control group.…”

“…The possible longterm effects and the unpredictable duration are controversial and matters of debate [13,48]. Repeated use of corticosteroids especially could facilitate tissue atrophy, joint destruction, or cartilage degeneration [9,15,35].…”

Quantitative T2 mapping of femoral head cartilage in systemic lupus erythematosus patients with noncollapsed osteonecrosis of the femoral head associated with corticosteroid therapy

“…Farkas et al (32) reported that glucocorticoids and local anesthetics induced apoptosis in chondrocytes especially in the superficial layer of the osteochondral specimens. Fubini et al (33) also suggested that methylprednisolone suppressed matrix protein markers of chondrocytic differentiation and that the altered chondrocyte expression of matrix proteins likely contributed to the pathogenesis of corticosteroid-induced cartilage degeneration. On the other hand, Vos et al (34) reported that the plasma level of human cartilage glycoprotein was increased in inflammatory conditions such as SLE with and without joint disease.…”

Bupivacaine and Triamcinolone May Be Toxic To Human Chondrocytes: A Pilot Study

“…Triamcinolone, a commonly used intraarticular corticosteroid [8,42], is clinically nondeleterious [37]. Although some studies show slowing of mechanically and chemically induced degeneration on a gross level [33,34,43], others have found histologic evidence of chondrotoxicity from corticosteroids in experimental models [7,19,32,39]. However, these studies did not evaluate buffering of the reagents to a physiologic pH and they were not performed on human cartilage.…”