New Findings in Muscle Injury—An Under-Researched Subject

Periostin for OBuzzThe goal of orthopaedic surgery is to help the entire musculoskeletal system function in harmony, but the preponderance of orthopaedic research focuses on the skeletal system instead of muscles and tendons. Bone is the only organ that can heal by regenerating tissue that is usually just as effective as the original structure. Consequently, we have focused on developing systems to hold bone intact as it heals so that postinjury function is maximized. Decades have been spent understanding the critical biologic pathways of bone healing and developing implantable, pharmacologic, and cell-based therapies to optimize it.

However, we sometimes overlook the fact that the skeleton can’t move without muscles. Only a few researchers have devoted their careers to understanding skeletal muscle’s response to injury and approaches to enhance muscle recovery after disuse and injury. In the August 15, 2018 issue of The Journal, Hara et al. report on experiments with the protein periostin in mice. Periostin is involved with the process of muscle fibrosis, during which fibroblasts proliferate in the injured area of the muscle and create “scar tissue” that eventually inhibits muscle function.

In one experiment, the authors found that “knockout” mice without the gene that encodes for periostin had improved recovery in a lacerated gastrocnemius muscle, less fibrosis in the muscle, and a significantly reduced number of infiltrating fibroblasts than “wild” mice with the same induced injury. In a similar experiment, they found reduced muscle fibrosis in injured muscles of mice whose production of periostin was neutralized by an antibody injected into the injured muscle. Although a sharp injury to muscle (the laceration model used in these mouse experiments) is not a common clinical scenario in patients seen by orthopaedists, the Hara et al. study represents a step forward in understanding muscle response to injury.

While these findings need to be replicated and then translated into clinical applications for humans, they shed new light on the importance of preventing periostin-induced fibroblast migration after skeletal muscle injury. This research hints at a potential therapeutic strategy to enhance muscle’s functional recovery, which is the most sought-after outcome for patients.

The clinical sports and orthopaedic communities are in need of approaches to limit scarring and atrophy in the setting of muscle disuse and injury. Any of us who unavoidably injure muscle during surgical approaches to bones and joints or for graft harvests and other procedures should be heartened by these findings. It is my hope that more early-career researchers will focus on the first half of the term “musculoskeletal” to advance therapeutic approaches to problems that impact function to a much more permanent degree than do most bone injuries.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

2 thoughts on “New Findings in Muscle Injury—An Under-Researched Subject

  1. Important aspect.
    Furthermore, not only can the skeleton not move without muscles, but circulation also depends on muscle function. For example, venous backflow in the lower extremities is greatly enhanced by forceful ankle and toe movements (Kropp et al., 2017). This pumping action (Gardner and Fox RH, 2001) would not be not possible in the case of calf muscle scarring and atrophy.

    -Kropp AT et al. The efficacy of forceful ankle and toe exercises to increase venous return – A comprehensive Doppler ultrasound study. Phlebology. 2018 Jun;33(5):330-337.

    – Gardner AMN and Fox RH. The venous system in health and disease, 3rd ed. Amsterdam: IOS Press, 2001.

  2. Evolution of healing is considerably cleverer as a method than the crude interventions of orthopaedic surgeons. It would be unwise to jump to clinical conclusions just yet on the basis of an experiment in mice that cuts, rather than tears (as in human injuries), muscle fibres.

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