Superoxide Mediates Shock Wave Induction of ERK-dependent Osteogenic Transcription Factor (CBFA1) and Mesenchymal Cell Differentiation toward Osteoprogenitors

Abstract

؊ by superoxide dismutase and inhibition of ERK activation by PD98059 decreased specific osteogenic transcription factor, core binding factor A1 activation, and decreased osteocalcin expression. Taken together, we showed that ESW-induced O 2 ؊ production followed by tyrosine kinase-mediated ERK activation and core binding factor A1 activation resulted in osteogenic cell growth and maturation. Thus, an appropriate modulation of redox reaction by ESW may have some positive effect on the bone regeneration.Oxidative stress induced by superoxide has been implicated in the induction of certain cell injury (1-5). In contrast, superoxide also plays an important role in the regulation of cell proliferation and metabolism (6 -8). Several physical factors such as heat (9), electrical field (10), pulsatile stretch (11), and laser irradiation (12) can stimulate cell proliferation through the involvement of superoxide. It is not known whether superoxide can regulate osteoprogenitor cell growth and differentiation.Extracorporeal shock wave (ESW) 1 is created by a high voltage spark discharge under water causing an explosive evaporation of water and producing high energy acoustic waves. The acoustic waves are focused on a semi-ellipsoid reflector and therefore can be transmitted into a specific tissue site (13). ESW treatment has been divergently applied for eukaryotic and prokaryotic biology systems. It is well known that ESW provides a non-invasive biophysical strategy for breaking renal stones with minimal side effects (13). Evidence also suggests that shock waves can potentially enhance gene transfer (14), suppress tumor growth (15), and promote the bactericidal effect of microorganisms (16).Recently, we and others (17)(18)(19)(20) have shown that ESW treatment has a promising effect on the promotion of bone fracture healing and repair of tendinitis. The mechanism by which ESW enhances fracture healing and repair of tendinitis remains to be determined. The fact that ESW treatment enhances both bone and tendon regeneration suggests that ESW may induce a certain signal for growth and maturation of the mesenchymal progenitors from bone marrow. It has been well clarified that the differentiation and maturation of bone marrow mesenchymal osteoprogenitor cells into osteoblastic lineage is involved in bone regeneration (21)(22)(23). In support of the hypothesis, we have recently shown ESW treatment to be able to promote bone marrow stromal cell growth and differentiation toward osteogenic lineage, presumably through TGF-␤1 induction (24).Accumulated evidence suggests that ESW induces a cavitation effect to increase membrane permeability and the influx of biological substances (25,26), which are usually implicated in cell and tissue damage (15,27). There is limited evidence showing that ESW promotes cell growth rather than cell damage. We hypothesized in this study that an optimal ESW treatment promoted osteoprogenitor cell growth and maturation via a rapid induction of oxygen radicals for a signal transduction

Recruitment of mesenchymal stem cells and expression of TGF‐β1 and VEGF in the early stage of shock wave‐promoted bone regeneration of segmental defect in rats

“…We recently have found that bone morphogenetic proteins (BMPs) are actively involved in ESW-promoted healing of segmental defects [44]. Osteogenic transcription factor (CbfallRunx2) and Indian hedgehog (Ihh) are further candidates to mediate chondrogenic and osteogenic differentiation of mesenchymal stem cells after ESW treatment [43].…”

Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

“…[31] ERK can stimulate the osteoblast-related gene expression by extracellular matrix-integrin receptor interaction, BMP-2, growth factors, and mechanostressing. [31][32][33][34] Xiao et al [35] demonstrated that stimulation of MAPK enhances the expression of osteocalcin, whereas the ERK-specific inhibitor (PD98059) inhibits expression. Our data show that PD98059 significantly inhibits AOPP-induced calcium deposition and OPN expression, indicating that AOPP can promote osteoblast differentiation and calcification of HASMCs via the ERK pathway.…”

Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1/2-Runx2 signaling

“…ALP activity of the cell lysate was measured using p-nitrophenylphosphate (pNPP), as described previously (15). ALP activity was expressed as nmol p-nitrophenol produced per min/mg of total protein.…”