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Effects of crystalline glucocorticoid triamcinolone acetonide on cultered human supraspinatus tendon cells.

ABSTRACT: BACKGROUND: Rotator cuff tears are a common cause of shoulder pain and impairment. Subacromial glucocorticoid injections are widely used for treatment of epiphenomenons of chronic impingement syndrome with the possible side effects of tendon rupture and impaired tendon healing. METHODS: Using qRT-PCR, western blot, immunoflourescence, and measurement of 3H-thymidine uptake we investigated the effects of the crystalline glucocorticoid triamcinolone acetonide (TAA) when added to the culture medium of isolated human rotator cuff tendon cells. RESULTS: After 2 weeks of incubation, the cells had lost their fibroblastic appearance and parallel orientation, which is characteristic of cellular degeneration in vivo. Moreover, expression and secretion of collagen I was strongly reduced, and there was a decrease in proliferation rate. Cell migration was blocked and the rate of expression of the matrix metalloproteinases MMP2, MMP8, MMP9, and MMP13 was reduced, but expression of TIMP1 (a tissue inhibitor of MMPs) was upregulated, indicating a reduction in the cellular capacity for tendon repair. In addition, changes in cellular differentiation were observed: the number of adipocytes increased and levels of the protein Sox9-a marker of differentiating and mature chondrocytes-were elevated in triamcinolone acetonide treated cells. INTERPRETATION: These results may indicate that the use of TAA is one reason for weaker mechanical tendon properties and for the high rate of re-rupture after supraspinatus tendon repair.

SUBMITTER: Tempfer H

PROVIDER: S-EPMC2823208 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Effects of crystalline glucocorticoid triamcinolone acetonide on cultered human supraspinatus tendon cells.

Tempfer Herbert H Gehwolf Renate R Lehner Christine C Wagner Andrea A Mtsariashvili Maia M Bauer Hans-Christian HC Resch Herbert H Tauber Mark M

Acta orthopaedica 20090601 3

<h4>Background</h4>Rotator cuff tears are a common cause of shoulder pain and impairment. Subacromial glucocorticoid injections are widely used for treatment of epiphenomenons of chronic impingement syndrome with the possible side effects of tendon rupture and impaired tendon healing.<h4>Methods</h4>Using qRT-PCR, western blot, immunoflourescence, and measurement of 3H-thymidine uptake we investigated the effects of the crystalline glucocorticoid triamcinolone acetonide (TAA) when added to the c ...[more]

PMID: 19421912

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Project description:BackgroundIntra-articular corticosteroids are commonly used for pain relief in patients with knee osteoarthritis. Simultaneous intra-articular corticosteroid (CS) knee injections may be beneficial for the ~80-90% of patients who present with, or develop, bilateral knee osteoarthritis, but concurrent injections may increase systemic CS exposure and data on safety/tolerability are lacking. Triamcinolone acetonide extended release (TA-ER) has shown decreased systemic triamcinolone acetonide exposure compared with traditional triamcinolone acetonide crystalline suspension (TAcs) after a single knee injection in patients with knee osteoarthritis. This phase IIa study was designed to assess the safety and systemic triamcinolone acetonide exposure following injections of TA-ER or TAcs into each knee of patients with bilateral knee osteoarthritis.MethodsPatients (⩾40 years) meeting American College of Rheumatology criteria for knee osteoarthritis in both knees received concurrent single intra-articular injections of TA-ER 32 mg or TAcs 40 mg into each knee (total: 64 mg and 80 mg, respectively) and were followed for 6 weeks. Safety was evaluated based on treatment-emergent adverse events (TEAEs). Blood samples for pharmacokinetic analysis were collected pre-injection, and at the following postinjection time points: 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 h, and days 8, 15, 29, and 43.ResultsBaseline characteristics were balanced between patients randomly assigned to TA-ER (n = 12) or TAcs (n = 12). Both treatments were well tolerated with comparable TEAE profiles. Peak plasma triamcinolone acetonide concentrations (Cmax) were lower following bilateral TA-ER injections [geometric mean, 2277.7 pg/ml (95% CI, 1602.13-3238.04)] compared with bilateral TAcs injections [7394.7 pg/ml (2201.06-24,843.43)], with median times to Cmax (Tmax) of 4.5 and 6.5 h, respectively.ConclusionsIn patients with bilateral knee osteoarthritis, intra-articular injection of TA-ER into both knees was well tolerated. Consistent with pharmacokinetic profiles observed after a single knee injection, plasma triamcinolone acetonide concentrations were lower after bilateral TA-ER injections compared with the higher and more variable concentrations observed after bilateral TAcs injections.Clinicaltrialsgov identifierNCT03378076.

Dataset Information

Effects of crystalline glucocorticoid triamcinolone acetonide on cultered human supraspinatus tendon cells.

Publications

Effects of crystalline glucocorticoid triamcinolone acetonide on cultered human supraspinatus tendon cells.

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