ESWT has been shown to have great potentional in promoting the osteogensis of bone marrow mesenchymal stem cells

Focal Adhesion Kinase Signaling
Mediated the Enhancement
of Osteogenesis of Human
Mesenchymal Stem Cells Induced
by Extracorporeal Shockwave
Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis
of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic
promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs)
and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the
osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate
the underlying mechanisms. We show here that ESW (0.16mj/mm2) significantly promoted the
osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of
miR-138, but the activation of FAK, ERK1/2, and RUNX2. The enhancement of osteogenesis in these
MSCs was consistently abolished when the cells were pretreated with one of the following conditions:
overexpression of miR-138, FAK knockdown using specific siRNA, and U0126, implying that all of these
elements are indispensable for mediating the effect of ESW. Moreover, our study provides converging
genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally
activated in ESW-preconditioned MSCs, suggesting that ESW may be a promising therapeutic strategy
for the enhancement of osteogenesis of MSCs, regardless of their origins.
Extracorporeal shockwave (ESW) has been widely used in musculoskeletal disorders such as bone defects
(delayed- and non-union of bone fractures, avascular necrosis of femoral head), with a success rate around 80%,
while the complications are low or negligible1
. ESW in orthopaedics is not used to disintegrate tissues, rather to
induce tissue repair and regeneration2
. Several ESW devices have been approved by the United States Food and
Drug Administration (FDA) as Class III orthopedic lithotripsy devices3

Eswt stem cells
.
ESW causes both direct (physical) and indirect (biological) effects on the interfaces of treated tissue. Regarding
the physical effects, both the positive and the negative phase of ESW have effects on tissues4
. However, it seems that
the biological effects of ESW, which transduce the mechanical signals into biological signals, is more crucial for the
tissue repair. Mechanotransduction stimulates extracellular matrix binding proteins and the nucleus via the cytoskeleton resulting in response leading to tissue regeneration. Several previous studies have demonstrated that ESW
promotes bone healing through a typical biological response characterized by the up-regulation of bone growth
factors, bone morphogenetic proteins5–7, and the activities of extracellular signal-regulated kinases (ERKs) and kinase8
. It has also been reported that an ESW treatment at 0.16mJ/mm2 for 500 impulses induce osteogenesis in
vitro partially through a rapid membrane hyperpolarization and activation of Ras9
. The trabecular bone volume
fraction and trabecular thickness of the treated calcaneus were significantly enhanced by ESW in an ovariectomized
goat model10. Moreover, clinical patients with fracture nonunion have been also benefiting from ESW treatment11,12.

Eswt stem cells