Muscle cells play a vital role in repairing fractured bones, according to a recent study published in the journal Bone Research. This groundbreaking research reveals an unexpected role of muscle-resident fibroadipogenic progenitors (FAPs) and superficial periosteal cells in the healing process. The study, led by Dr. Ugur M. Ayturk, highlights the potential of these cells as therapeutic targets to enhance fracture healing and prevent unwanted bone growth.
The study found that FAPs, which reside in skeletal muscle, and superficial periosteal cells, found in the thin connective tissue covering bones, remain dormant under normal conditions. However, after injury, these cells are recruited to help repair fractured bones. The researchers used Clec3b expression as a highly specific marker for these normally dormant progenitor cells, allowing them to track their location and response after injury.
During normal bone growth, these cells remained in muscle and the superficial periosteum and never migrated into bone or differentiated into osteoblasts. However, following bone fractures, these cells rapidly migrated to the injury site, where many differentiated into osteoblasts that produced new bone and aided in the healing process. Within three weeks, the researchers found that about 28% of the osteoblasts in the healing callus originated from Clec3b-lineage cells. Some of these cells also became bone marrow stromal cells, which helped rebuild the supportive environment inside the bone.
The study also confirmed this transition using single-cell RNA sequencing, showing that dormant Clec3b-lineage cells gave rise to new populations with the molecular characteristics of bone marrow stromal cells and osteoblasts after fracture. Furthermore, the researchers investigated the origin of these bone-forming cells and found that skeletal muscle is the main source. Even after the periosteum was surgically removed before injury, Clec3b-positive cells still reached the fracture site and developed into bone-forming cells.
The cells were also found to contribute to heterotopic ossification, a condition in which bone forms in muscles and other soft tissues after injury. In mouse models, Clec3b-lineage cells differentiated into cartilage- and bone-forming cells, becoming a major source of this abnormal bone. When a key pathway required for bone formation was blocked or these cells were depleted, both fracture healing and abnormal bone growth were significantly reduced.
Dr. Ayturk believes that these cells could become promising therapeutic targets. Activating them may enhance fracture healing, while limiting their bone-forming activity could help prevent unwanted bone growth following serious injuries. This research opens up new avenues for understanding and treating bone injuries, potentially leading to improved healing outcomes and reduced complications.
