Short-wave enhances mesenchymal stem cell recruitment in fracture healing by increasing HIF-1 in callus

Abstract

Background As a type of high-frequency electrotherapy, a short-wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms remain unclear. Purpose To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing. Materials and methods For in vivo study, the effect of Short-Wave therapy to fracture healing was examined in a stabilized femur fracture model of 40 SD rats. Radiography was used to analyze the morphology and microarchitecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot. Results Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Wave therapy upregulated HIF-1 and SDF-1 expression in osteoblast and its cultured medium, as well as the expression of CXCR-4, β-catenin, F-actin, and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC. Conclusions These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

[Retracted] Downregulation of miR‐221‐3p by LncRNA TUG1 Promoting the Healing of Closed Tibial Fractures in Mice

“…Further study revealed that compared with siLncRNA TUG1 and miR-221-3p overexpression groups, the Bcl-2 level in the LncRNA TUG1 group was higher, with remarkably lower SDF-1 level in the miR-221-3p overexpression group than those in the control, miRNA-NC, and LncRNA TUG1 groups. SDF-1, a part of the α chemokine family, whose specific receptor CXCR4 is expressed on the surface of many cells, and the two can constitute the SDF-1/CXCR4 axis, serving as a key part in tissue injury and bone damage repair [21][22][23]. Clinical studies have shown that the secretion of SDF-1 in the bone repair site increases, and CXCR4 +-committed stem cells around bone marrow, peripheral circulating blood, and soft tissue of bone trauma migrate to the bone injury site along the gradient of SDF-1 concentration to participate in bone healing [24].…”

Melatonin Accelerates Osteoporotic Bone Defect Repair by Promoting Osteogenesis–Angiogenesis Coupling

“…The repair of bone defects requires recapitulation of complex signaling cascades, including a series of spatiotemporal angiogenesis and osteogenesis ( 34 , 35 ). However, for osteoporosis, the bone resorption rate is greater than that of new bone formation, with a decreased ability for new bone formation.…”

Construction of Vascularized Tissue Engineered Bone with nHA-Coated BCP Bioceramics Loaded with Peripheral Blood-Derived MSC and EPC to Repair Large Segmental Femoral Bone Defect

“…Bone defect repair is a complex signaling cascade involving spatiotemporal osteogenesis and angiogenesis, both of which require stem/progenitor cell migration and osteogenic differentiation, accompanied by ordered angiogenesis. , Exogenous osteogenic and angiogenic stimulating factors may cause imbalance in bone formation, leading to excessive bone formation or vascular leakage, and even the risk of tumor . Therefore, there is a need to increase osteogenesis and angiogenesis through potential, endogenous, and balanced stimulation.…”