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Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification
Article first published online: 18 APR 2012
DOI: 10.1002/jbmr.1562
Copyright © 2012 American Society for Bone and Mineral Research
Additional Information
How to Cite
Wosczyna, M. N., Biswas, A. A., Cogswell, C. A. and Goldhamer, D. J. (2012), Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification. J Bone Miner Res, 27: 1004–1017. doi: 10.1002/jbmr.1562
Publication History
- Issue published online: 18 APR 2012
- Article first published online: 18 APR 2012
- Accepted manuscript online: 3 FEB 2012 11:12AM EST
- Manuscript Accepted: 25 JAN 2012
- Manuscript Revised: 23 JAN 2012
- Manuscript Received: 8 DEC 2011
References
- 1
- 2, , , , Heterotopic ossification following traumatic and combat-related amputations. Prevalence, risk factors, and preliminary results of excision. J Bone Joint Surg Am. 2007; 89(3): 476–86.
- 3, Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP). Bone. 2008; 43(3): 427–33.
- 4, , , , Heterotopic ossification in the residual limbs of traumatic and combat-related amputees. J Am Acad Orthop Surg. 2006; 14( 10 Suppl): S191–7.
- 5, Heterotopic ossification: a review. J Rehabil Med. 2005; 37(3): 129–36.
- 6, , , , , , , , , In vivo somatic cell gene transfer of an engineered Noggin mutein prevents BMP4-induced heterotopic ossification. J Bone Joint Surg Am. 2003; 85-A(12): 2332–42.
- 7, , , Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype. Am J Pathol. 2004; 165(4): 1107–15.
- 8Animal models of heterotopic ossification. Clin Orthop. 1998; 346: 71–80.
- 9, Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop. 1998; 346: 26–37.
- 10, , , Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science. 1998; 280(5368): 1455–7.
- 11, , , , , , , , Cytokine expression in muscle following traumatic injury. J Orthop Res. 2011; 29(10): 1613–20.
- 12, , , , , , , , , BMP-9-induced muscle heterotopic ossification requires changes to the skeletal muscle microenvironment. J Bone Miner Res. 2011; 26(6): 1166–77.
- 13, , , Expression of bone morphogenetic proteins and rat distal-less homolog genes following rat femoral fracture. J Bone Miner Metab. 2000; 18(2): 63–70.
- 14, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J Biol Chem. 2009; 284(11): 7149–56.
- 15, , , Heterotopic ossification. J Am Acad Orthop Surg. 2004; 12(2): 116–25.
- 16, , , , , De novo 617G-A nucleotide mutation in the ACVR1 gene in a Taiwanese patient with fibrodysplasia ossificans progressiva. J Hum Genet. 2006; 51(12): 1083–6.
- 17, , , , , The ACVR1 617G>A mutation is also recurrent in three Japanese patients with fibrodysplasia ossificans progressiva. J Hum Genet. 2007; 52(5): 473–5.
- 18, , , , , , , , , , , , , , , , , A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006; 38(5): 525–7.
- 19, , , , , , , , Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP). J Bone Miner Res. 2008; 23(3): 305–13.
- 20, , , , , , , Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP). J Bone Miner Metab. 2008; 26(6): 521–30.
- 21Bone: formation by autoinduction. Science. 1965; 150(698): 893–9.
- 22, , , , Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice. Biochem Biophys Res Commun. 2007; 354(2): 453–8.
- 23, , , , Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway. Stem Cells. 2008; 26(1): 223–34.
- 24, , , , , , , , Hematopoietic stem-cell contribution to ectopic skeletogenesis. J Bone Joint Surg Am. 2007; 89(2): 347–57.
- 25, , , , , , , , Circulating osteogenic precursor cells in heterotopic bone formation. Stem Cells. 2009; 27(9): 2209–19.
- 26, , , , , , Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells. 2009; 27(1): 150–6.
- 27, , , , , , , , , Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol. 1994; 127(6 Pt 1): 1755–66. [Published erratum appears in J Cell Biol 1995 Feb;128(4):following 713.]
- 28, , , , Generation of different fates from multipotent muscle stem cells. Development. 2002; 129(12): 2987–95.
- 29, , , , , , , , Identification of progenitor cells that contribute to heterotopic skeletogenesis. J Bone Joint Surg Am. 2009; 91(3): 652–63.
- 30, , , , , Conversion of vascular endothelial cells into multipotent stem-like cells. Nat Med. 2010; 16(12): 1400–6.
- 31, , , , , Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. Dev Biol. 2001; 230(2): 230–42.
- 32, , , , , , , VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells. Dev Dyn. 2006; 235(3): 759–67.
- 33, , , , , , A multifunctional reporter mouse line for Cre- and FLP-dependent lineage analysis. Genesis. 2009; 47(2): 107–14.
- 34, , , , , , The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002; 108(1): 17–29.
- 35, , L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway. Osteoarthritis Cartilage. 2001; 9( Suppl A): S69–75.
- 36, , , Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system. Proc Natl Acad Sci U S A. 1993; 90(20): 9355–8.
- 37, , , , , , Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell. 2005; 8(3): 211–26.
- 38, , , , , Molecular cloning and characterization of mouse TIE and TEK receptor tyrosine kinase genes and their expression in hematopoietic stem cells. Biochem Biophys Res Commun. 1993; 195(1): 301–9.
- 39, , , , Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat Cell Biol. 2010; 12(2): 143–52.
- 40, , , , , , , Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat Cell Biol. 2010; 12(2): 153–63.
- 41, , , , , , , , , , , , , , Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci U S A. 2011; 108(1): 143–8.
- 42, , Identification of white adipocyte progenitor cells in vivo. Cell. 2008; 135(2): 240–9.
- 43, , , , , , , Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nat Cell biol. 2010; 12(3): 257–66.
- 44, , , , , , , Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration [see comments]. J Cell Biol. 1999; 147(4): 869–78.
- 45, , , , , , , Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999; 401(6751): 390–4.
- 46, , , , , , , , , , Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J Cell Biol. 2002; 157(5): 851–64.
- 47, , , , , , Functional heterogeneity of side population cells in skeletal muscle. Biochem Biophys Res Commun. 2006; 341(3): 864–73.
- 48, , , , Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet. Stem Cells. 2009; 27(10): 2563–70.
- 49, , , , , , , Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol. 2008; 22(1): 191–205.
- 50, , , , , , , , , , , , , , BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008; 14(12): 1363–9.
- 51, , , , , , Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva [see comments]. N Engl J Med. 1996; 335(8): 555–61.
- 52, , , , , , , , , , , , , , , , , , , Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. 2009; 30(3): 379–90.Direct Link:
- 53, Mechanisms of muscle degeneration, regeneration, and repair in the muscular dystrophies. Annu Rev Physiol. 2009; 71: 37–57.

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