Shock Wave Treatment Enhances Cell Proliferation and Improves Wound Healing by ATP Release-coupled Extracellular Signal-regulated Kinase (ERK) Activation

Abstract

Background: Signaling pathways underlying beneficial effects of extracorporeal shock wave treatment (ESWT) remain to be completely elucidated. Results: ESWT enhances cell proliferation in vitro and wound healing in vivo. Conclusion: ESWT-induced ATP release and subsequent extracellular signal-regulated kinase (ERK) activation are prerequisites for enhanced cell proliferation and wound healing. Significance: Deciphering the involved signaling cascades provides the basis for ESWT as clinical wound healing treatment.

Extracorporeal shockwave therapy (ESWT) – First choice treatment of fracture non-unions?

“…Further intracellular participants of the signaling cascade triggered by various stimuli (e.g. ATP [10][11][12], integrin [7], radicals [13;14]) in response to extracorporeal shockwave therapy include the p38 MAPK, ERK1/2 [11-13;15], and AKT [8] pathway.…”

Extracorporeal shockwave therapy (ESWT) ameliorates healing of tibial fracture non-union unresponsive to conventional therapy

“…Via a mechanism known as mechanotransduction [31] shockwaves are transduced into biochemical signals affecting multiple endogenous pathways. To illustrate, ATP triggered ERK1/2 pathway activation improves cell proliferation and wound healing [32,33], and modulation of the inflammatory process via TLR3 [34] and other molecular signals [35,36] seem to accelerate wound healing. Biological responses induced by ESWT include angio-and lymphogenesis [36][37][38][39][40][41][42][43]; recruitment, proliferation and differentiation of endogenous stem cells [42,[44][45][46][47]; osteogenesis [48][49][50][51][52][53].…”

Blast Loading of Cells

“…13 for a comprehensive review]. More recently, it has been shown that shock waves trigger the release of cellular adenosine triphosphate (ATP), causing activation of Erk1/2 signalling pathway [17]. These biological responses are generally viewed as favourable for enabling soft tissue wound healing by promoting appropriate levels of inflammation, neo-vascularisation and tissue repair mechanisms [13].…”