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phosphodiesterase activity causing an increase in intracellular cAMP levels by stimulat-
ing the cAMP-dependent protein kinase pathway. This increase in cAMP levels is sub-
sequently responsible for the synthesis of lipogenic enzymes during adipogenesis
(Spiegelman and Green 1981 ; Tang and Lane 2012 ). Ali and colleagues have shown that
the removal of IBMX from the induction medium almost completely blocks the nor-
mally observed increase in intracellular lipid accumulation (Ali et al. 2006 ). Insulin acts
as a potent adipogenic hormone by triggering the induction of a series of transcription
factor, which facilitate differentiation of preadipocytes into mature adipocytes via the
insulin-like growth factor 1 (IGF-1) receptor (Ntambi and Young-Cheul 2000 ).
Dexamethasone is a synthetic glucocorticoid agonist used to stimulate the glucocorti-
coid receptor pathway. Although each agent is able to initiate adipogenesis, an additive
effect is observed when the factors are combined (Russell and Ho 1976 ; Rubin et al.
1978 ). Please refer to the supplementary material for a brief description of the method
used to induce adipogenesis in vitro.
Fig. 7.1 Regulation of ASC differentiation. Fat accumulation, cartilage formation, bone forma-
tion and bone resorption are closely related. Adipocytes, osteoblasts and chondrocytes have a
common origin, the mesenchymal stem cell, while osteoclasts originate from the haematopoietic
stem cell. Osteoblasts regulate bone resorption through the RANKL/RANK/OPG pathway.
Osteoblast differentiation is regulated by RUNX2. Key regulators of adipogenesis are PPAR-γ and
C/EBP. Adipocytes secrete inflammatory cytokines and hormones which are capable of modulat-
ing bone formation. Chondrogenesis is mainly regulated by BMPs, TGF-β and Sox9. Modified
from Fig. 7.1 in Cao ( 2011 ) and Rosen and Bouxsein ( 2006 ). RUNX2 runt-related transcription
factor 2, RANK/RANKL receptor activator of nuclear factor-kB ligand, OPG osteoprotegerin,
PPAR-γ peroxisome proliferator-activated receptor-γ, C/EBP CCAAT/enhancer-binding proteins,
BMP bone morphogenetic protein, TGF transforming growth factor, Sox sex-determining region
Y-type high mobility group box (Cao 2011 ; Rosen and Bouxsein 2006 )
F.A. van Vollenstee et al.