Identification and Characterization of an Injury-induced Skeletal Progenitor

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Jul 29

PMID 26216955

Citations 65

Authors

Owen Marecic

Ruth Tevlin

Adrian McArdle

Eun Young Seo

Taylor Wearda

Christopher Duldulao

Graham G Walmsley

Allison Nguyen

Irving L Weissman

Charles K F Chan

Michael T Longaker

Affiliations

Soon will be listed here.

Abstract

The postnatal skeleton undergoes growth, remodeling, and repair. We hypothesized that skeletal progenitor cells active during these disparate phases are genetically and phenotypically distinct. We identified a highly potent regenerative cell type that we term the fracture-induced bone, cartilage, stromal progenitor (f-BCSP) in the fracture callus of adult mice. The f-BCSP possesses significantly enhanced skeletogenic potential compared with BCSPs harvested from uninjured bone. It also recapitulates many gene expression patterns involved in perinatal skeletogenesis. Our results indicate that the skeletal progenitor population is functionally stratified, containing distinct subsets responsible for growth, regeneration, and repair. Furthermore, our findings suggest that injury-induced changes to the skeletal stem and progenitor microenvironments could activate these cells and enhance their regenerative potential.

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References

Slack J . Stem cells in epithelial tissues. Science. 2000; 287(5457):1431-3. DOI: 10.1126/science.287.5457.1431. View

Rinkevich Y, Montoro D, Contreras-Trujillo H, Harari-Steinberg O, Newman A, Tsai J . In vivo clonal analysis reveals lineage-restricted progenitor characteristics in mammalian kidney development, maintenance, and regeneration. Cell Rep. 2014; 7(4):1270-83. PMC: 4425291. DOI: 10.1016/j.celrep.2014.04.018. View

Wagers A, Allsopp R, Weissman I . Changes in integrin expression are associated with altered homing properties of Lin(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) hematopoietic stem cells following mobilization by cyclophosphamide/granulocyte colony-stimulating factor. Exp Hematol. 2002; 30(2):176-85. DOI: 10.1016/s0301-472x(01)00777-9. View

Anderson R, Lawrence A, Stottmann R, Bachiller D, Klingensmith J . Chordin and noggin promote organizing centers of forebrain development in the mouse. Development. 2002; 129(21):4975-87. DOI: 10.1242/dev.129.21.4975. View

Garvey W, Fathi A, BIGELOW F, Carpenter B, Jimenez C . Improved Movat pentachrome stain. Stain Technol. 1986; 61(1):60-2. DOI: 10.3109/10520298609110708. View

Spangrude G, Heimfeld S, Weissman I . Purification and characterization of mouse hematopoietic stem cells. Science. 1988; 241(4861):58-62. DOI: 10.1126/science.2898810. View

Mendelson A, Frenette P . Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med. 2014; 20(8):833-46. PMC: 4459580. DOI: 10.1038/nm.3647. View

Zhou B, Yue R, Murphy M, Peyer J, Morrison S . Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell. 2014; 15(2):154-68. PMC: 4127103. DOI: 10.1016/j.stem.2014.06.008. View

Amano K, Densmore M, Nishimura R, Lanske B . Indian hedgehog signaling regulates transcription and expression of collagen type X via Runx2/Smads interactions. J Biol Chem. 2014; 289(36):24898-910. PMC: 4155658. DOI: 10.1074/jbc.M114.570507. View

10.

Chen L, Kostadima M, Martens J, Canu G, Garcia S, Turro E . Transcriptional diversity during lineage commitment of human blood progenitors. Science. 2014; 345(6204):1251033. PMC: 4254742. DOI: 10.1126/science.1251033. View

11.

Jin H, Wang B, Li J, Xie W, Mao Q, Li S . Anti-DKK1 antibody promotes bone fracture healing through activation of β-catenin signaling. Bone. 2014; 71:63-75. PMC: 4376475. DOI: 10.1016/j.bone.2014.07.039. View

12.

Adhami M, Rashid H, Chen H, Clarke J, Yang Y, Javed A . Loss of Runx2 in committed osteoblasts impairs postnatal skeletogenesis. J Bone Miner Res. 2014; 30(1):71-82. PMC: 4280286. DOI: 10.1002/jbmr.2321. View

13.

Amanai K, Jiang J . Distinct roles of Central missing and Dispatched in sending the Hedgehog signal. Development. 2001; 128(24):5119-27. DOI: 10.1242/dev.128.24.5119. View

14.

Morrison S, Weissman I . Heterogeneity of hematopoietic stem cells: implications for clinical applications. Proc Assoc Am Physicians. 1995; 107(2):187-94. View

15.

Mitchell M, Logan P . Radiation-induced changes in bone. Radiographics. 1998; 18(5):1125-36; quiz 1242-3. DOI: 10.1148/radiographics.18.5.9747611. View

16.

Sherwood R, Christensen J, Conboy I, Conboy M, Rando T, Weissman I . Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell. 2004; 119(4):543-54. DOI: 10.1016/j.cell.2004.10.021. View

17.

Yang W, Yang D, Na S, Sandusky G, Zhang Q, Zhao G . Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem. 2004; 280(10):9330-5. DOI: 10.1074/jbc.M413394200. View

18.

Bryder D, Rossi D, Weissman I . Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol. 2006; 169(2):338-46. PMC: 1698791. DOI: 10.2353/ajpath.2006.060312. View

19.

Chan C, Chen C, Luppen C, Kim J, DeBoer A, Wei K . Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature. 2008; 457(7228):490-4. PMC: 2648141. DOI: 10.1038/nature07547. View

20.

Cho S, Yang J, Sun H, Jung J, Her S, Cho H . Wnt inhibitory factor (WIF)-1 inhibits osteoblastic differentiation in mouse embryonic mesenchymal cells. Bone. 2009; 44(6):1069-77. DOI: 10.1016/j.bone.2009.02.012. View