Inhibition of tendon cell migration by dexamethasone is correlated with reduced alpha-smooth muscle actin gene expression: a potential mechanism of delayed tendon healing.
Local corticosteroid injection is commonly used to treat sports-related tendon injuries. However, isolated cases of tendon rupture following injection suggest that this treatment may impair the healing process. Tendon healing requires the migration of tendon cells to the repair site, followed by the proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of dexamethasone on the migration of tendon cells intrinsic to rat Achilles tendon at concentrations similar to those typically used for local injection treatment. Furthermore, the existence of a correlation between this effect and the expression of the contractile actin isoform, alpha-smooth muscle (SM) actin, which is associated with cell motility, was also examined. Using cultured tendon cells, migration was evaluated by counting the number of initial outgrowths from the tendon explants and by transwell filter migration assay. The distribution and assembly of alpha-SM actin were assessed by immunocytochemistry. The mRNA and protein expressions of alpha-SM actin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Dose-dependent dexamethasone inhibition was demonstrated for both tendon cells outgrowth from the explants, ex vivo, and migration of tendon cells through the transwell filter, in vitro. Immunocytochemical staining revealed significant decreases in both the amount and assembly of alpha-SM actin in cells. Suppression of mRNA expression and protein level of alpha-SM actin was revealed from RT-PCR and Western blot analyses. In conclusion, dexamethasone inhibits tendon cell migration that is correlated with decreased gene expression of alpha-SM actin.
Tsai
Wen-Chung
WC
Department of Physical Medicine and Rehabilitation, Graduate Institute of Clinical Medical Sciences, Chang Gung Memorial Hospital, Chang Gung University, Building J, 12F, 5 Fu-Shin Street, Gueishan, Taoyuan, Taiwan.
Tang
Fuk-Tan
FT
Wong
May-Kuen
MK
Pang
Jong-Hwei S
JH
D000125:Achilles Tendon / Q000166:cytology / Q000187:drug effects*; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000502:physiology*
D000199:Actins; D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone