Glucocorticoids suppress proteoglycan production by human tenocytes.

BACKGROUND: The role of glucocortiocid injection therapy in spontaneous tendon rupture is controversial. We hypothesized that glucocorticoids suppress proteoglycan production in tendon and studied the in vitro effects of dexamethasone and triamcinolone on proteoglycan production by cultured human tenocytes. MATERIAL AND METHODS: We obtained primary cultures of human tenocytes from explants of healthy human patellar tendon. The human tenocytes were treated with 1 microM dexamethasone or 1 microM triamcinolone. The amount of proteoglycan production was measured by 35S-sulfate incorporation assay and compared with control cultures. The reversibility of the effect of dexamethasone by co-incubation with 10 ng platelet-derived growth factor (PDGFBB) was also tested. RESULTS: Treatment with 1 microM triamcinolone reduced the amount of 35S-sulfate incorporation to 80% of control cultures (p = 0.007), whereas 1 microM dexamethasone reduced it to 72% (p = 0.01). Co-incubation of 10 ng/mL PDGFBB with 1 microM dexamethasone returned the 35S-sulfate incorporation to a level that was significantly higher than for dexamethasone treatment alone (108%; p = 0.01). INTERPRETATION: Glucocorticoids suppressed proteoglycan production in cultured human tenocytes. The suppression by dexamethasone was reversed by simultaneous addition of PDGFBB. Suppressed proteoglycan production may affect the viscoelastic properties of tendon and increase the risk of spontaneous rupture.

Effect of dexamethasone on cultured human tenocytes and its reversibility by platelet-derived growth factor.

BACKGROUND: Many cases of tendon rupture after glucocorticoid injections have been reported in the literature. Despite previous studies on the histological and biomechanical changes in tendons after glucocorticoid injections, the role of glucocorticoid in causing tendon rupture still remains controversial. The objective of this study was to determine whether glucocorticoid has deleterious effects on the cellular metabolism and collagen production of cultured human tenocytes and the reversibility of these effects by platelet-derived growth factor-BB (PDGFBB). METHODS: Primary cultures of human tenocytes obtained from explants of healthy patellar tendon, harvested during anterior cruciate ligament reconstructions, were performed. The effects on cell viability, cell proliferation, and induction of apoptosis were measured by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, 5-bromo-deoxyuridine incorporation, and DNA fragmentation assay, respectively. The effect on collagen synthesis was measured by (3) H-proline incorporation assay. RESULTS: The number of viable cells was decreased, in a dose-dependent manner, by the administration of 10 (-9) to 10 (-4) -M dexamethasone. This dose range also suppressed cell proliferation. No apoptotic effect was detected. Treatment with 10 (-6) -M dexamethasone significantly reduced the amount of collagen synthesis. Co-incubation with 10 ng/mL of PDGFBB significantly reversed the effects caused by 10 (-6) -M dexamethasone. CONCLUSIONS: Dexamethasone significantly decreased cell viability, suppressed cell proliferation, and reduced collagen synthesis in cultured human tenocytes. The effects were reversed by the simultaneous administration of PDGFBB.