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PMID:22510437

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Citation

Takimoto, A, Oro, M, Hiraki, Y and Shukunami, C (2012) Direct conversion of tenocytes into chondrocytes by Sox9. Exp. Cell Res. 318:1492-507

Abstract

Sox9 is a high-mobility group box-containing transcription factor that functions as a key regulator of chondrogenesis. We here report that Sox9 mediates the direct conversion of tenocytes to chondrocytes through an intermediate state in which both differentiation programs are active. Sox9 is abundantly expressed in cartilage but is undetectable in limb tendons that express Scleraxis (Scx) and Tenomodulin (Tnmd), tendon-specific early and late molecular markers, respectively. Upon forced expression of Sox9 in the chick forelimb, ectopic cartilage formation is preferentially observed in fibrous tissues including the tendons, ligaments, perichondrium/periosteum, dermis, and muscle connective tissues. Tnmd expression in tenocytes isolated from leg tendons was markedly upregulated by forced expression of basic helix-loop-helix (b-HLH) activators including Scx, Paraxis, Twist1 and Twist2. In contrast, the overexpression of Sox9 in monolayer tenocytes resulted in the downregulation of Tnmd and Scx expressions during passaging in culture, and the induction of cartilage molecular markers such as type II collagen (Col2a1) and Chondromodulin-I (ChM-I). This Sox9-driven switching from a tenocytic to a chondrocytic gene expression profile was associated with a dramatic change from a spindle to a polygonal cellular morphology. The extracellular accumulation of cartilage-characteristic proteoglycans was also observed. These data suggest that tenocytes have a strong potential for conversion into chondrocytes through the activities of Sox9 both in vitro and in vivo.

Links

PubMed Online version:10.1016/j.yexcr.2012.04.002

Keywords

Animals; Avian Proteins/genetics; Avian Proteins/metabolism; Base Sequence; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism; Cell Differentiation/genetics; Cell Differentiation/physiology; Cell Transdifferentiation/genetics; Cell Transdifferentiation/physiology; Cells, Cultured; Chick Embryo; Chondrocytes/cytology; Chondrocytes/metabolism; Chondrogenesis/genetics; Chondrogenesis/physiology; Choristoma/genetics; Choristoma/metabolism; Choristoma/pathology; DNA Primers/genetics; Fibroblasts/cytology; Fibroblasts/metabolism; Gene Expression Regulation, Developmental; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism; Mice; Mice, Inbred C57BL; Myoblasts/cytology; Myoblasts/metabolism; Osteoblasts/cytology; Osteoblasts/metabolism; SOX9 Transcription Factor/genetics; SOX9 Transcription Factor/metabolism; Tendons/cytology; Tendons/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CHICK:C4P6Q3

involved_in

GO:0060290: transdifferentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000388)
  • results_in_commitment_to:(CL:0000056)

Seeded From UniProt

complete

CHICK:C4P6Q3

involved_in

GO:0045445: myoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:MYOG

involved_in

GO:0045445: myoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:SOX9

involved_in

GO:0002062: chondrocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:Q8UVG3

involved_in

GO:0001649: osteoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:Q8UWC8

involved_in

GO:0001649: osteoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:MYOG

involved_in

GO:0045445: myoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:MYOG

involved_in

GO:0060290: transdifferentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000388)
  • results_in_commitment_to:(CL:0000056)

Seeded From UniProt

complete

CHICK:SOX9

involved_in

GO:0002062: chondrocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:SOX9

involved_in

GO:0060290: transdifferentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000388)
  • results_in_commitment_to:(CL:0000138)

Seeded From UniProt

complete

CHICK:SOX9

involved_in

GO:1903011: negative regulation of bone development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:O73668

involved_in

GO:0002062: chondrocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:O73668

involved_in

GO:0060290: transdifferentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000388)
  • results_in_commitment_to:(CL:0000138)

Seeded From UniProt

complete

CHICK:O73668

involved_in

GO:1903011: negative regulation of bone development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q8UVG3

involved_in

GO:0001649: osteoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

CHICK:Q8UWC8

involved_in

GO:0001649: osteoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(UBERON:0010328)

Seeded From UniProt

complete

Notes

See also

References

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