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.
Wong
Margaret Wan Nar
MW
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin. mwnwong@cuhk.edu.hk
Tang
Yvonne Yin Nei
YY
Lee
Simon Kwong Man
SK
Fu
Bruma Sai Chuen
BS
Chan
Barbara Pui
BP
Chan
Cavor Kai Ming
CK
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D013710:Tendons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D003907:Dexamethasone; D003094:Collagen