Chondrocytes Transdifferentiate into Osteoblasts in Endochondral Bone during Development, Postnatal Growth and Fracture Healing in Mice

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During endochondral bone formation, which is responsible for the generation of most bones in mammals and many other species, osteoblasts deposit a bone-specific matrix on the surface of cartilage scaffolds made by chondrocytes and hypertrophic chondrocytes. It has long been thought that the terminally differentiated chondrocytes in this cartilage scaffold undergo cell death. Here we demonstrate that chondrocytes can transdifferentiate into osteoblasts and that these transdifferentiated osteoblasts represent a substantial fraction of the bone forming cells in mice, We also provide evidence that chondrocytes can transdifferentiate into osteoblasts during bone fracture repair, a process similar to endochondral bone formation.

Vyšlo v časopise: Chondrocytes Transdifferentiate into Osteoblasts in Endochondral Bone during Development, Postnatal Growth and Fracture Healing in Mice. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004820
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004820

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1. Akiyama H, de Crombrugghe B (2009) Transcription control of chondrocyte differentiation. The skeletal system: Cold spring harbor laboratory press. pp. 147–170.

2. MackieEJ, AhmedYA, TatarczuchL, ChenKS, MiramsM (2008) Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol 40 : 46–62.

3. MaesC, KobayashiT, SeligMK, TorrekensS, RothSI, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell 19 : 329–344.

4. ClarkinC, OlsenBR On bone-forming cells and blood vessels in bone development. Cell Metab 12 : 314–316.

5. GerstenfeldLC, ShapiroFD (1996) Expression of bone-specific genes by hypertrophic chondrocytes: implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development. J Cell Biochem 62 : 1–9.

6. BiancoP, CanceddaFD, RiminucciM, CanceddaR (1998) Bone formation via cartilage models: the “borderline” chondrocyte. Matrix Biol 17 : 185–192.

7. KirschT, SwobodaB, von der MarkK (1992) Ascorbate independent differentiation of human chondrocytes in vitro: simultaneous expression of types I and X collagen and matrix mineralization. Differentiation 52 : 89–100.

8. RoachHI, ErenpreisaJ, AignerT (1995) Osteogenic differentiation of hypertrophic chondrocytes involves asymmetric cell divisions and apoptosis. J Cell Biol 131 : 483–494.

9. ErenpreisaJ, RoachHI (1996) Epigenetic selection as a possible component of transdifferentiation. Further study of the commitment of hypertrophic chondrocytes to become osteocytes. Mech Ageing Dev 87 : 165–182.

10. RoachHI (1997) New aspects of endochondral ossification in the chick: chondrocyte apoptosis, bone formation by former chondrocytes, and acid phosphatase activity in the endochondral bone matrix. J Bone Miner Res 12 : 795–805.

11. ShapiroIM, AdamsCS, FreemanT, SrinivasV (2005) Fate of the hypertrophic chondrocyte: microenvironmental perspectives on apoptosis and survival in the epiphyseal growth plate. Birth Defects Res C Embryo Today 75 : 330–339.

12. ColnotC, LuC, HuD, HelmsJA (2004) Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol 269 : 55–69.

13. MayeP, FuY, ButlerDL, ChokalingamK, LiuY, et al. Generation and characterization of Col10a1-mcherry reporter mice. Genesis 49 : 410–418.

14. KomoriT, YagiH, NomuraS, YamaguchiA, SasakiK, et al. (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89 : 755–764.

15. OttoF, ThornellAP, CromptonT, DenzelA, GilmourKC, et al. (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89 : 765–771.

16. NakashimaK, ZhouX, KunkelG, ZhangZ, DengJM, et al. (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108 : 17–29.

17. ZhouX, ZhangZ, FengJQ, DusevichVM, SinhaK, et al. Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice. Proc Natl Acad Sci U S A 107 : 12919–12924.

18. GebhardS, HattoriT, BauerE, SchlundB, BoslMR, et al. (2008) Specific expression of Cre recombinase in hypertrophic cartilage under the control of a BAC-Col10a1 promoter. Matrix Biol 27 : 693–699.

19. HenrySP, JangCW, DengJM, ZhangZ, BehringerRR, et al. (2009) Generation of aggrecan-CreERT2 knockin mice for inducible Cre activity in adult cartilage. Genesis 47 : 805–814.

20. MaoX, FujiwaraY, ChapdelaineA, YangH, OrkinSH (2001) Activation of EGFP expression by Cre-mediated excision in a new ROSA26 reporter mouse strain. Blood 97 : 324–326.

21. SorianoP (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21 : 70–71.

22. ShanerNC, CampbellRE, SteinbachPA, GiepmansBN, PalmerAE, et al. (2004) Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22 : 1567–1572.

23. AkiyamaH, KimJE, NakashimaK, BalmesG, IwaiN, et al. (2005) Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proc Natl Acad Sci U S A 102 : 14665–14670.

24. KalajzicZ, LiuP, KalajzicI, DuZ, BrautA, et al. (2002) Directing the expression of a green fluorescent protein transgene in differentiated osteoblasts: comparison between rat type I collagen and rat osteocalcin promoters. Bone 31 : 654–660.

25. SchindelerA, McDonaldMM, BokkoP, LittleDG (2008) Bone remodeling during fracture repair: The cellular picture. Semin Cell Dev Biol 19 : 459–466.

26. GerstenfeldLC, CullinaneDM, BarnesGL, GravesDT, EinhornTA (2003) Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 88 : 873–884.

27. DayTF, GuoX, Garrett-BealL, YangY (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8 : 739–750.

28. HillTP, SpaterD, TaketoMM, BirchmeierW, HartmannC (2005) Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8 : 727–738.

29. RoddaSJ, McMahonAP (2006) Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133 : 3231–3244.

30. HuH, HiltonMJ, TuX, YuK, OrnitzDM, et al. (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132 : 49–60.

31. Akiyama H, de Crombrugghe B (2009) Transcription control of chondrocyte differentiation. The skeletal system: Cold spring harbor laboratory press. pp. 147–170.

32. JoplingC, BoueS, Izpisua BelmonteJC Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nat Rev Mol Cell Biol 12 : 79–89.

33. TsonisPA, MadhavanM, TancousEE, Del Rio-TsonisK (2004) A newt's eye view of lens regeneration. Int J Dev Biol 48 : 975–980.

34. van der KraanPM, van den BergWB (2007) Osteophytes: relevance and biology. Osteoarthritis Cartilage 15 : 237–244.

35. RamirezDM, RamirezMR, ReginatoAM, MediciD (2014) Molecular and cellular mechanisms of heterotopic ossification. Histol Histopathol

36. ShoreEM, KaplanFS (2010) Inherited human diseases of heterotopic bone formation. Nat Rev Rheumatol 6 : 518–527.

37. YangL, TsangKY, TangHC, ChanD, CheahKS (2014) Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc Natl Acad Sci U S A 111 : 12097–12102.

38. FuX, SunH, KleinWH, MuX (2006) Beta-catenin is essential for lamination but not neurogenesis in mouse retinal development. Dev Biol 299 : 424–437.

39. JiangX, KalajzicZ, MayeP, BrautA, BellizziJ, et al. (2005) Histological analysis of GFP expression in murine bone. J Histochem Cytochem 53 : 593–602.