title: Myogenic progenitors contribute to open but not closed fracture repair.
abstract: BACKGROUND
  Bone 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Renjing
authors.initials: R
authors.lastname: Liu
authors.forename: Oliver
authors.initials: O
authors.lastname: Birke
authors.forename: Alyson
authors.initials: A
authors.lastname: Morse
authors.forename: Lauren
authors.initials: L
authors.lastname: Peacock
authors.forename: Kathy
authors.initials: K
authors.lastname: Mikulec
authors.forename: David G
authors.initials: DG
authors.lastname: Little
authors.forename: Aaron
authors.initials: A
authors.lastname: Schindeler
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage; D054338:Cell Transdifferentiation; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D017102:Fracture Healing; D005596:Fractures, Closed / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005597:Fractures, Open / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017930:Genes, Reporter; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017570:MyoD Protein / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013977:Tibia / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D013978:Tibial Fractures / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D017570:MyoD Protein; C045073:Cre recombinase; D019426:Integrases; D000469:Alkaline Phosphatase