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

Abstract

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 3H-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. Clinical Relevance: The current study demonstrates that glucocorticoids adversely affect human tenocytes in cell culture. As the effects are reversible with simultaneous administration of PDGFBB, the growth factor may be useful clinically as a protective agent for patients receiving local glucocorticoid injections.