Biomedical Engineering Reference
In-Depth Information
neoplastic diseases, and autoimmune disorders. Currently, vari-
ous forms of glucocorticoids with varying half-lives, potentencies,
and receptor a
nities have been developed for clinical use. These
drugs include dexamethasone, betamethasone, hydrocortisone, and
prednisone.
97
Unfortunately, administration of excess amounts of
glucocorticoids frequently results in detrimental effects on the
skeleton, namely glucocorticoid-induced osteoporosis (GIO).
98
,
99
Glucocorticoids reduce bone formation by decreasing osteoblast
proliferation and terminal differentiation, as well as by promoting
apoptosis of osteocytes, resulting in the development of GIO.
100
,
101
In an
in vitro
MSC culture system, glucocorticoids act as both
osteogenic and adipogenic factors. The bifunctional effects of gluco-
corticoids are dependent on dosage: at high concentrations (about
10
-
6
M),MSCsrespondtodexamethasonebydifferentiatingintothe
adipocyte lineage, while at lower doses (about 10
-
8
M), MSCs dif-
ferentiateintotheosteoblastlineage.Underconditionsfavorablefor
differentiationintotheosteoblastlineage,dexamethasonedecreases
MSC proliferation and triggers osteogenesis through the expres-
sionofmultipleosteogenicmarkers,includingalkalinephosphatase
(ALP), osteocalcin, and many other osteoblast-related genes.
102
-
106
In the case of MSCs obtained from adipose tissue, treatment with
glucocorticoids, such as dexamethasone, betamethasone, hydrocor-
tisone, and prednisone, has a negligible effect on proliferation.
43
In
addition to growth suppression, glucocorticoids also inhibit the ter-
minal differentiation of MSCs and promote apoptosis of osteoblasts
and mature osteocytes.
100
,
101
Concisely, glucocorticoids can inhibit
proliferation of MSCs and influence the differentiation of MSCs
into either the osteoblast or adipocyte lineage, depending on the
dosage.
41.2.3
Combination of Growth Factors and Steroids
While synthetic glucocorticoids are suppressors of MSC growth and
inducersofMSCdifferentiation,growthfactorsareessentialforopti-
mal growth of MSCs
in vitro
. However, when these two factors are
combined, a significant enhancement of both MSC growth as well as
MSC differentiation occurs.
Search WWH ::
Custom Search