Extracorporeal shock wave therapy (ESWT) is increasingly recognized as a promising non-invasive therapeutic modality within orthopedic regenerative medicine. ESWT has increased adoption due to its ability to induce biological responses essential for bone repair. However, the molecular and cellular mechanisms underlying its osteogenic effects remain incompletely understood. This narrative review aims to comprehensively describe these critical mechanisms and explore their implications for therapeutic practice. A comprehensive narrative literature review was conducted to synthesize current evidence on the molecular and cellular pathways activated by ESWT. Searches were performed across MEDLINE/ PubMed, Scopus, Embase, and additional databases from January 1990 through September 2024. Emphasis was placed on mechanotransduction, angiogenesis, stem cell dynamics, immunomodulation, extracellular matrix (ECM) remodeling, and osteoclast regulation. A total of 30 studies met the inclusion criteria and were analyzed in detail. ESWT promotes osteogenesis mainly through mechanotransduction pathways involving integrin-mediated MAPK/ERK and Wnt/β-catenin signaling, enhancing osteoblast proliferation and differentiation. It also stimulates angiogenesis via upregulation of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), improving vascularization necessary for bone healing. ESWT boosts mesenchymal stem cell recruitment, proliferation, and osteogenic differentiation through ATP signaling and elevated growth factors (BMPs, TGF-β1). Additionally, it modulates immune responses by reducing pro-inflammatory cytokines and fostering anti-inflammatory macrophage polarization. ESWT further aids ECM remodeling by increasing collagen synthesis and regulating matrix metalloproteinases, creating an optimal structure for bone regeneration, while inhibiting osteoclast differentiation to limit bone resorption. Understanding these molecular and cellular pathways reinforces the clinical efficacy of ESWT and underscores the importance of optimizing therapeutic protocols. These insights could potentially aid orthopedic regenerative treatments by enabling more precise, targeted applications of ESWT for bone repair.
Mechanisms underlying ESWT-induced osteogenesis: a review of molecular and cellular pathways / Pezone, F.; Biavardi, N. G.; D'Andrea, G.; Placella, G.; Alessio-Mazzola, M.; Salini, V.. - In: MINERVA ORTHOPEDICS. - ISSN 2784-8469. - 76:3(2025), pp. 253-262. [10.23736/S2784-8469.25.04599-7]
Mechanisms underlying ESWT-induced osteogenesis: a review of molecular and cellular pathways
Pezone F.;Biavardi N. G.;Placella G.;Salini V.
2025-01-01
Abstract
Extracorporeal shock wave therapy (ESWT) is increasingly recognized as a promising non-invasive therapeutic modality within orthopedic regenerative medicine. ESWT has increased adoption due to its ability to induce biological responses essential for bone repair. However, the molecular and cellular mechanisms underlying its osteogenic effects remain incompletely understood. This narrative review aims to comprehensively describe these critical mechanisms and explore their implications for therapeutic practice. A comprehensive narrative literature review was conducted to synthesize current evidence on the molecular and cellular pathways activated by ESWT. Searches were performed across MEDLINE/ PubMed, Scopus, Embase, and additional databases from January 1990 through September 2024. Emphasis was placed on mechanotransduction, angiogenesis, stem cell dynamics, immunomodulation, extracellular matrix (ECM) remodeling, and osteoclast regulation. A total of 30 studies met the inclusion criteria and were analyzed in detail. ESWT promotes osteogenesis mainly through mechanotransduction pathways involving integrin-mediated MAPK/ERK and Wnt/β-catenin signaling, enhancing osteoblast proliferation and differentiation. It also stimulates angiogenesis via upregulation of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), improving vascularization necessary for bone healing. ESWT boosts mesenchymal stem cell recruitment, proliferation, and osteogenic differentiation through ATP signaling and elevated growth factors (BMPs, TGF-β1). Additionally, it modulates immune responses by reducing pro-inflammatory cytokines and fostering anti-inflammatory macrophage polarization. ESWT further aids ECM remodeling by increasing collagen synthesis and regulating matrix metalloproteinases, creating an optimal structure for bone regeneration, while inhibiting osteoclast differentiation to limit bone resorption. Understanding these molecular and cellular pathways reinforces the clinical efficacy of ESWT and underscores the importance of optimizing therapeutic protocols. These insights could potentially aid orthopedic regenerative treatments by enabling more precise, targeted applications of ESWT for bone repair.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
