Chronic Inflammation Changes the Cellular Responses of the Myofascia

Abstract

BACKGROUNDTissue texture changes are associated with musculoskeletal injury. Osteopathic Manipulative Medicine (OMM) uses these changes to diagnosis and treat musculoskeletal injury. OMM has been well documented in the treatment of myofascial pain and remains a popular treatment option despite a lack of knowledge regarding the molecular mechanisms underlying these tissue changes. Tumor necrosis factor a (TNF‐a) is a proinflammatory cytokine that has been linked to muscle wasting and is released following injury. Previous OMM studies have provided evidence of the important role fibroblasts play in restoration of skeletal muscle after injury and cell‐cell interaction during the repair process7. Therefore, we hypothesize that chronic inflammation affects the phenotype of the myofascia and leads to patient pain. To study the molecular mechanisms underlying myofascial pain, we examined the main cells that compromise the myofascia, primary human skeletal muscle cells and human dermal fibroblasts.METHODSWe assessed human skeletal muscle cells and human dermal fibroblast cells in an in vitro model. Each cell type was exposed to varying doses of recombinant TNF‐a for five days, after which we measured the phenotypic effects of the pro‐inflammatory cytokine on the cells using light microscopy images and cell count.RESULTSIn the absence of TNF‐a, human skeletal muscle cells have a distinct spindle shape. The control cells proliferate in such a way that many cells do not require cell‐cell contact and are very evenly dispersed. However, in the presence of TNF‐a, human skeletal muscle cell phenotype was visually distinct in which the cells grew in discrete sections, some sections were circular in nature, with very tight cell‐cell contact. Our data also revealed that human fibroblasts experienced dose dependent phenotypic changes in response to TNF‐a. Specifically, when compared with the control, fibroblast cells exhibited significant phenotypic change from diamond shaped to elongated spindle shaped cells in a dose dependent manner.Secondly, we measured cell count with increasing dosage of TNF‐a. We found a decrease in human skeletal muscle cell count in a dose‐dependent manner when exposed to TNF‐a. In contrast, our data depicted fibroblast increased cell growth and proliferation with exposure to increasing TNF‐aquantities.CONCLUSIONAlthough osteopathic medicine is known to improve pain, there is limited evidence of the precise cellular mechanisms of how OMT works. Our results indicate that exposure to inflammation changes the phenotype of the myofascia leading to the formation of fibrotic tissue. Studies have shown that fibroblasts respond to injury by rapid proliferation at the site of injury, forming granulation tissue. These changes support the hypothesis that exposure to chronic inflammation changes the phenotype of the myofascia and provide structural integrity to the wound1. Based on our results, we found that when exposed to TNF‐α, human dermal fibroblasts and human skeletal muscle cells exhibit opposite responses to inflammation. That is, fibroblasts have increased cell growth when exposed to increasing TNF‐α, while human skeletal muscle cells have decreased cell growth with exposure to TNF‐α.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.