Abstract
BackgroundBone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.MethodsWe employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a human alkaline phosphatase (hAP) reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.ResultsIn the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP+ cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP+ cells detected in the open fracture callus. At early stages of repair, many hAP+ cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP+ cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP+ staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.ConclusionsThese data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery.Please see related article: http://www.biomedcentral.com/1741-7015/9/136
Highlights
Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone
The conventional cellular understanding of the bone repair process places progenitors originating from the periosteum and the bone marrow compartment in a pivotal role
We have recently reviewed a range of progenitor cell types that may have the potential to contribute to bone repair [4]
Summary
Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. We have recently reviewed a range of progenitor cell types that may have the potential to contribute to bone repair [4] These include cells from the adjacent soft tissues (myogenic progenitors, vascular endothelial cells, and pericytes) as well as circulating progenitors. When bone repair is observed in the clinical orthopaedic setting, the bone that first forms in response to a fracture is often seen adjacent to the local muscles [8]. Such data is only circumstantial and does not demonstrate that myogenic cells can contribute to bone formation in an in vivo setting
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