The Effects of Dexamethasone on Human
Patellar Tendon Stem Cells: Implications for Dexamethasone Treatment of Tendon

Zhang J,
Keenan C, Wang J H-C. J Orthopaed Res. 2012; [Epub ahead of print].

is a clinical diagnosis characterized by focal tenderness, activity-related
pain, weakness, and increased tendon size. 
Unlike the commonly used term “tendinitis” suggests, inflammation is not
normally seen in the late stages of tendinopathy but may be present in early
stages.  Clinically, despite lack of
evidence of inflammation in chronic tendinopathy, prescription of glucocorticoids,
such as Dexamethasone, is often used as a quick-fix to
reduce pain and “inflammation”; however, some studies suggest that
administration of such drugs may worsen tendon degeneration.  Tendon stem cell differentiation into non-tenocytes may contribute to
the progression of tendon degeneration. 
The authors of this article were interested in the effects of
Dexamethasone specifically on tendon stem cells to suggest a cause for Dexamethasone-induced
tendon damage.  Human tendon stem cells were
isolated from patellar tendons (7 donors), cultured in growth medium, and
confirmed to be stem cells.  Cells were
divided into 5 groups: control and 5, 10, 100, and 1000 nM Dexamethasone
administration for 1 week.  Tendon stem
cell proliferation and differentiation were assessed.  Target genes included collagen
type I
(tenocytes), PPARγ (adipocytes), Sox-9 (chondrocytes), and Runx-2 (osteocytes).  In vivo
experiments involved subcutaneous implantation of cells cultured for 1 week in
0, 10, 100, or 1000 nM Dexamethasone with Matrigel (mixture that mimics extracellular
matrix of many tissues) into female nude rats. 
Three weeks following implantation, tissue was harvested for
histological analysis and stained with Oil Red O (adipose-like), Safranin O
(cartilage-like), and Alizarin Red S (bone-like).  In
results showed that cell proliferation was dose-dependent: low
concentrations of Dexamethasone increased cell proliferation, but high
concentrations decreased proliferation.  Collagen
I expression was drastically diminished in all four groups of cells treated
with Dexamethasone compared to control.  PPARγ
(adipogenesis) and Sox-9 (chondrogenesis) expression increased with increasing
concentration of Dexamethasone; Runx-2 (osteogenesis) expression remained
unchanged.  In vivo analysis demonstrated increased fatty, cartilage-like, and
bone-like tissue formed from cells treated with Dexamethasone compared to

findings of this study suggest that Dexamethasone treatment may impair tendon healing.  Specifically, Dexamethasone appears to
increase tendon stem cell differentiation into non-tenocytes and reduce
collagen I production, which could exasperate the injury.  This study opens the door for future studies
to investigate the mechanisms responsible for these observations.  This study investigated only tendon stem
cells, and the effects on tenocytes, the predominant tendon cell, still need to
be identified.  Furthermore, cells were
taken from uninjured tendons, which may not properly mimic the cells inhabiting
tendinopathic tissue or surgically repaired healing tissue.  The authors chose to implant cells
subcutaneously, which also may not accurately mimic the environment—mechanical
and biological—of tendon.  Finally, cells
were cultured in Dexamethasone for 1 week prior to implantation, meaning that
at implantation, the groups started from a different point, so end point
comparisons may not be completely fair. 
Regardless of these limitations, the results of this study give clear
indication that Dexamethasone as a treatment for tendon disorders may need to
be reconsidered.  Does this work impact
your clinical recommendations?  Do you
prescribe Dexamethasone for tendon degeneration, and if so, will you continue?  Do you think that Dexamethasone may have a
different effect in tendons with early tendinopathy than chronic? 

by: Sarah Ilkhani-Pour
by: Stephen Thomas


Zhang J, Keenan C, & Wang JH (2012). The effects of dexamethasone on human patellar tendon stem cells: Implications for dexamethasone treatment of tendon injury. Journal of Orthopaedic Research PMID: 22886634