Acute Inflammatory Response in Osteoporotic Fracture Healing Augmented with Mechanical Stimulation is Regulated In Vivo through the p38-MAPK Pathway.

Simon Kwoon Ho Chow,Keith Yu Kin Cheng,Jinyu Wang,Wing Hoi Cheung,Ronald Man Yeung Wong,Yu Ning Chim,Carissa Hing Wai Wong,Ka Wai Ng,Can Cui

doi:10.3390/ijms22168720

Simon Kwoon Ho Chow, Keith Yu Kin Cheng + Show 7 more

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https://doi.org/10.3390/ijms22168720

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Abstract

Low-magnitude high-frequency vibration (LMHFV) has previously been reported to modulate the acute inflammatory response of ovariectomy-induced osteoporotic fracture healing. However, the underlying mechanisms are not clear. In the present study, we investigated the effect of LMHFV on the inflammatory response and the role of the p38 MAPK mechanical signaling pathway in macrophages during the healing process. A closed femoral fracture SD rat model was used. In vivo results showed that LMHFV enhanced activation of the p38 MAPK pathway at the fracture site. The acute inflammatory response, expression of inflammatory cytokines, and callus formation were suppressed in vivo by p38 MAPK inhibition. However, LMHFV did not show direct in vitro enhancement effects on the polarization of RAW264.7 macrophage from the M1 to M2 phenotype, but instead promoted macrophage enlargement and transformation to dendritic monocytes. The present study demonstrated that p38 MAPK modulated the enhancement effects of mechanical stimulation in vivo only. LMHFV may not have exerted its enhancement effects directly on macrophage, but the exact mechanism may have taken a different pathway that requires further investigation in the various subsets of immune cells.

Highlights

Osteoporotic fracture is an emerging problem in older adults in the developed world and accounts for a high proportion of medical care costs worldwide
We found that the p-p38 level was markedly increased in the OVX-vibration group (VT) group at weeks 1 and 2 compared to the OVX group (Figure 1a, p = 0.029 and p = 0.000, respectively), suggesting that Low-magnitude high-frequency vibration (LMHFV) was able to activate p38 MAPK at the fracture site in ovariectomized bones
This study focused on the potential roles of the p38 MAPK signaling pathway in LMHFV-augmented osteoporotic fracture healing. p38 MAPK has been reported to play important roles in inflammatory response, as well as bone development and remodeling, but its role in fracture healing has not been well understood

Summary

Introduction

Osteoporotic fracture is an emerging problem in older adults in the developed world and accounts for a high proportion of medical care costs worldwide. Fracture healing is a complex biological process that can coarsely be divided into three overlapping stages: inflammation, callus formation, and remodeling. The coordination of these processes determines the success of fracture healing. An inflammatory response is immediately casted to initiate and coordinate all the subsequent healing processes [6,7]. Different immune cells, such as macrophages, neutrophils, and lymphocytes, infiltrate the fracture site, and multiple inflammatory cytokines, including

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