Craniofacial Muscles

100 M. Lewis et al.
progenitors, a subpopulation of satellite cells, or an independent progenitor cell
population that is resident in the extracellular niche of skeletal muscle (McKinney-
Freeman et al. 2002 ) . Signi fi cantly, the potential to produce different tissues from
muscle-derived cells opens up another dimension for novel therapies, such as tissue
engineering (Qu-Petersen et al. 2002 ) .
Growth factors play a role in skeletal muscle development and growth. In particular,
insulin-like growth factors I and II (IGF-I and -II) play an important role in the
general growth and development of different tissues. The effects of IGFs, which are
under negative feedback, are initiated upon binding to cell surface receptors, which
are abundant in skeletal muscle (Livingston et al. 1988 ) , and modulated through
interactions with secreted IGF binding proteins (IGFBPs), of which there are six
members (Stewart and Rotwein 1996 ) . IGFBPs are secreted from cells that also
secrete IGFs (Ernst et al. 1992 ) , and it has been speculated that IGFBP-4 may be
necessary for in vivo enhancement of human skeletal muscle (Brimah et al. 2004 ) .
IGF-I appears to be essential for correct embryonic development in animal models,
as demonstrated by the underdeveloped muscle tissue and perinatal death of mice
homozygous for either a mutation of the IGF-I gene or IGF-I receptors (IGF-1Rs)
(Liu et al. 1993 ; Powell-Braxton et al. 1993 ) .
It is likely that the growth hormone (GH)–IGF axis plays a major part in mediating
the growth and differentiation of skeletal muscle. The direct action of GH is
unclear (Halevy et al. 1996 ) , despite establishing the presence of the GH receptor
mRNA in skeletal muscle. Data from recent studies in GH receptor knock-out mice
and established cell cultures have suggested that GH is not necessary for the control
of skeletal muscle during the embryonic and perinatal stages, but important for
postnatal myo fi bre growth involving the fusion of MPCs to nascent myotubes, as
well as the positive speci fi cation of type I fi bres (Sotiropoulos et al. 2006 ) . These
growth-enhancing actions of GH are facilitated by circulating or autocrine–paracrine
production of IGF-1 (Le Roith and Zick 2001 ) . Indeed, numerous studies have shown
increased IGF-1 mRNA within skeletal muscle tissue and MPC cell lines in response
to GH exposure (Florini et al. 1996 ) . There are three IGF-1 splice variants, IGF-
1Ea, IGF-1Eb and IGF-1Ec. Due to its upregulation in exercised and regenerating
human skeletal muscles, IGF-1Ec is also referred to as mechanogrowth factor
(MGF) (Yang et al. 1996 ) . IGF-1 is produced by MPCs within regenerating muscles
(Hawke and Garry 2001 ) , which promote MPC cell survival (Stewart and Rotwein
1996 ; Napier et al. 1999 ) , proliferation (Florini et al. 1996 ; Yang and Goldspink
2002 ; Ates et al. 2007 ) , differentiation (Galvin et al. 2003 ) , and hypertrophy (Baker
et al. 1993 ; Florini et al. 1996 ; Matsumoto et al. 2006 ; Quinn et al. 2007 ) , responses
that are temporally separate in MPCs (Allen and Boxhorn 1989 ; Florini et al. 1991 ) .
It has been demonstrated that MGF is upregulated after the surgical correction of
craniofacial abnormalities, thus indicating its role in regeneration and potential
adaptation in these specialised muscles (Maricic et al. 2008 ) .
Maximal stimulation of proliferation and the highest percentage of fusion of rat
satellite cells in vitro are produced by a combination of FGF and IGF-I (Allen and
Boxhorn 1989 ) ; however, differentiation with minimal proliferation can be achieved
with IGF-I alone. Proliferation is brought about by the activation of MAP kinases