With the global population aging rapidly, millions of joint replacement surgeries are performed each year. However, this common procedure carries the risk of a devastating complication: periprosthetic joint infection (PJI). When an implant becomes infected, bacteria like Staphylococcus aureus trigger massive host cell death. The immune system's failure to promptly clear these dead cells creates a toxic environment that sustains inflammation, hinders tissue repair, and allows the infection to persist, often leading to surgical failure.
While regular exercise is known to generally improve immune function, the exact molecular mechanisms bridging physical activity and localized immune defense in deep tissues like bones and joints have remained elusive. A breakthrough study published online on 29 April 2026 in the Journal of Sport and Health Science by researchers from Renji Hospital, Shanghai Jiao Tong University School of Medicine, has finally decoded this “molecular language.”
The research team, led by Dr. Bing Yue and Dr. Xinhua Qu, established a direct mechanistic link between regular treadmill exercise and enhanced host defense against PJI in murine models. Through comprehensive bulk RNA sequencing and proteomics, they identified “musclin”—a myokine secreted by skeletal muscles during contraction—as the critical messenger.
“ We found that injecting mice with musclin replicated the protective effects of regular exercise ,” said Dr. Zhiwei Fu, co-first author of the study. “ Musclin significantly reduced the bacterial load and mitigated inflammatory bone loss. It doesn't act as a traditional antibiotic to kill bacteria directly, but rather as a potent 'damage-control' signal that resets the local immune environment .”
The core mechanism uncovered by the team centers on a process called “efferocytosis”—the ability of macrophages to act as cellular scavengers and engulf dead, apoptotic cells. In a PJI microenvironment, this crucial function is severely impaired. The researchers discovered that circulating musclin binds directly to the formyl peptide receptor 2 (FPR2) on the surface of macrophages.
This specific ligand–receptor interaction triggers a profound metabolic reprogramming within the macrophages. It shifts the cells away from pathological, excessive glycolysis and restores functional mitochondrial oxidative phosphorylation (OXPHOS). This metabolic switch provides the necessary energy and signaling cues to drastically enhance the macrophages' efferocytosis capacity. By efficiently clearing the dead cellular debris, musclin breaks the vicious cycle of inflammation.
Furthermore, the study demonstrated substantial therapeutic potential when translating these findings into a treatment model. When musclin was administered alongside a conventional antibiotic (oxacillin), the combination therapy synergistically reduced bone destruction, suppressed tissue fibrosis, and successfully restored the adaptive immune response, outperforming antibiotic treatment alone.
This research highlights the musclin–FPR2–efferocytosis axis as a novel therapeutic target. “ Our findings provide scientific support for developing 'exercise-mimetic' host-directed immunotherapies ,” added the research team. “ For patients in the perioperative or rehabilitation phases of joint replacement, safely mimicking the physiological signals of exercise could offer a powerful new adjunctive strategy to combat challenging implant-associated infections .”
Reference
Title of original paper: Exercise-induced musclin enhances efferocytosis via metabolic reprogramming to alleviate periprosthetic joint infection
Journal: Journal of Sport and Health Science
DOI: https://doi.org/10.1016/j.jshs.2026.101143
About Bing Yue from Renji Hospital, Shanghai Jiao Tong University School of Medicine, China
Dr. Bing Yue is the Vice President of Renji Hospital and the Director of the Center for Sports System Diseases and Innovative Devices at Shanghai Jiao Tong University. He completed his joint Ph.D. training at Harvard Medical School. Dr. Yue is a recipient of the National Science Fund for Distinguished Young Scholars. His clinical and translational research focuses on quantitative techniques in joint arthroplasty and novel immune mechanisms in bone infections, with over 60 SCI publications.
About Xinhua Qu from Renji Hospital, Shanghai Jiao Tong University School of Medicine, China
Dr. Xinhua Qu is the Executive Director of the Department of Bone and Joint Surgery at Renji Hospital. As an outstanding researcher and clinician, he specializes in the translational research of bone and joint infectious diseases, osteoimmunology, and novel biomaterials. He leads multiple national projects including the Excellent Young Scientists Fund. Dr. Qu has published over 50 SCI papers in top-tier journals like Advanced Materials and is recognized among the World's Top 2% Scientists.
Funding information
This work was supported by the National Key Research and Development Program of China (2023YFC2509600); the National Natural Science Foundation of China (82225031, 82572782, 82402834); the Shanghai Shuguang Plan Project; the Shanghai Municipal Health Commission & Shanghai “Rising Stars of Medical Talent” Youth Development Program (20254Z0014); and the Innovative Research Team of High-Level Local Universities in Shanghai.
Journal of Sport and Health Science
Experimental study
Animals
Exercise-induced musclin enhances efferocytosis via metabolic reprogramming to alleviate periprosthetic joint infection
29-Apr-2026
The authors declare that they have no competing interests.