Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
The alchemy of tendon repair: a primer for the (S)mad scientist
Dwight A. Towler, Richard H. Gelberman
Dwight A. Towler, Richard H. Gelberman
Published April 3, 2006
Citation Information: J Clin Invest. 2006;116(4):863-866. https://doi.org/10.1172/JCI28320.
View: Text | PDF
Commentary

The alchemy of tendon repair: a primer for the (S)mad scientist

  • Text
  • PDF
Abstract

During vertebrate development, mesenchymal progenitors capable of forming bone, cartilage, muscle, fat, or tendon arise from either neural crest or somitic mesoderm. Transcriptional programs that specify mesenchymal cell fates are initiated and modified by paracrine cues provided by TGF-β superfamily members and mediated in part via the regulated assembly of Smad-containing multiprotein transcription factor complexes. In this issue of the JCI, Hoffmann and colleagues have identified that Smad8 activation drives tendon formation from C3H10T1/2 cells, a murine cell line that recapitulates many features of normal multipotent mesenchymal cells (see the related article beginning on page 940). Cells programmed to the tenocyte cell fate in vitro formed tenogenic grafts in vivo. These results add to the accumulating evidence that proliferating, multipotent mesenchymal progenitor cells can be programmed to yield multiple cell types — e.g., osteoblasts, myocytes, chondrocytes, and tenocytes — that may be useful in cell-based therapeutic approaches to musculoskeletal diseases.

Authors

Dwight A. Towler, Richard H. Gelberman

×

Figure 2

Lineage programming of mesenchymal progenitors: a working model.

Options: View larger image (or click on image) Download as PowerPoint
Lineage programming of mesenchymal progenitors: a working model.
(A) Dur...
(A) During development, mesenchymal progenitors capable of forming bone, cartilage, muscle, fat, or tendon arise from either neural crest or from mesoderm. Transcriptional programs (shown in italics) that specify mesenchymal cell fates are initiated and modified by paracrine cues provided by TGF-β superfamily members, mediated via regulated assembly of Smad-containing multiprotein transcription factor complexes (8). During somitic mesoderm lamination, the syndetome — demarcated by Scleraxis expression — forms at the interface between the bone-forming sclerotome and muscle-forming myotome to generate tenocytes of axial tendons (3). Similar mechanisms are likely deployed during appendicular tendon formation. Not shown are the influences of paracrine Wnt and FGF signaling cascades and homeodomain proteins of the Pax, Msx, Dlx, and Six families that modulate BMP signaling. The data reported by Hoffmann et al. (5) indicate that activated Smad8 promotes tenocyte differentiation of C3H10T1/2 cells. Whether Smad8 participates in syndetome development is unknown. C/EBP, CCAAT/enhancer binding protein; MRF, muscle regulatory factor; MRTF, myocardin-related transcription factor; SRF, serum response factor. (B) R-Smad and L+MH2 structures. Although the MH1 domain encodes a DNA-binding function, Smad interaction with other transcription factors is required for gene regulation; these interactions are directed by the L+MH2 domain (8). The SxS motif is the cognate for phosphorylation-dependent Smad activation by activin-like kinase receptors. Smad4 and importins mediate nuclear entry. Since the Smad8 L+MH2 fragment lacks intrinsic DNA binding, its tenogenic actions are mediated by regulatory protein-protein interactions.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts