Myogenic progenitors contribute to open but not closed fracture repair

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

Attenuated Human Bone Morphogenetic Protein-2–Mediated Bone Regeneration in a Rat Model of Composite Bone and Muscle Injury

“…[39][40][41][42] The contribution of musclederived cells to fracture healing was recently demonstrated by tracking muscle-derived cells (MyoD-Cre + ). 24 After a closed fracture, very few muscle-derived cells were present in the fracture callus, however, after an open fracture with the adjacent periosteum denuded, there was a substantial population of muscle-derived cells in the callus, fracture gap, and pericortical bone. 24 This study speculated that the periosteum is sufficient for fracture healing, and when present, other sources for osteoprogenitor cells are not necessary.…”

“…22,23 A recent study tracked these muscle progenitor cells after an open bone fracture and showed incorporation of these cells in regenerated bone. 24 These studies have demonstrated potential mechanisms of interaction between bone and muscle during regeneration.…”

Effect of Cell Origin and Timing of Delivery for Stem Cell-Based Bone Tissue Engineering Using Biologically Functionalized Hydrogels

“…37,51,52 The time point chosen in our delayed delivery study was selected based on the assumption that the presence of endogenous tissue in the defect site may facilitate nutrient and waste exchange of the delivered stem cells and facilitate recruitment of host progenitors before the degradation of BMP-2. However, given our results showing significantly less mineralized tissue in delayed samples compared with their immediate counterparts, our delivery time may have been too late.…”

Exercise and the skeleton: How it works and what it really does

“…Recently it was also shown that muscle can secrete growth factors such as IGF-1 and FGFs that would exert a paracrine role on periosteal cells (67). Muscle has also been suggested to contain a reserve of potential osteoprogenitor cells (68).…”