TGF-β, BMPs, and their signal transducing mediators, Smads, in rat fracture healing

Mark P. Ohan, Kevin S. Weadock, Michael Dunn

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Smads are cytoplasmic signal transducers of transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs). Their relation to fracture healing is unknown. This study examined the temporal protein expression of Smads, together with TGF-β and BMPs, using immunohistochemistry in a rodent fracture model. Over-expression of TGF-β, BMPs-2, 4, and 7, common-mediator Smad (Smad4), and receptor-regulated Smads (Smads1, 2, 3, and 5) versus lower levels of inhibitory Smad (Smad6), were detected at day 3 in osteogenic cells in the thickened periosteum and bone marrow at the fracture sites. At day 10, Smad6 increased dramatically, Smad2, Smad3, and Smad4 remained elevated while Smad1 and Smad5 decreased in the fracture callus. Smad7 was expressed only in vascular endothelial cells. By day 28, when new bone had replaced the fracture callus, all the protein regulators decreased, approaching control levels. During fracture healing, the expression patterns of Smads1 and 5 were similar to that of BMPs-2 and 7 whereas the expression of Smads2 and 3 was parallel with that of TGF-β. The Smad family, associated with BMPs and TGF-β, may play an important role in the early stage of rat fracture healing.

Original languageEnglish (US)
Pages (from-to)392-397
Number of pages6
JournalJournal of Biomedical Materials Research
Volume60
Issue number3
DOIs
StatePublished - Jun 5 2002

Fingerprint

Bone Morphogenetic Proteins
Transforming Growth Factors
Rats
Bone
Proteins
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein 7
Level control
Endothelial cells
Intercellular Signaling Peptides and Proteins
Transducers

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering

Keywords

  • BMPs
  • Fracture healing
  • Immunohistochemistry
  • Smads
  • TGF-β

Cite this

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abstract = "Smads are cytoplasmic signal transducers of transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs). Their relation to fracture healing is unknown. This study examined the temporal protein expression of Smads, together with TGF-β and BMPs, using immunohistochemistry in a rodent fracture model. Over-expression of TGF-β, BMPs-2, 4, and 7, common-mediator Smad (Smad4), and receptor-regulated Smads (Smads1, 2, 3, and 5) versus lower levels of inhibitory Smad (Smad6), were detected at day 3 in osteogenic cells in the thickened periosteum and bone marrow at the fracture sites. At day 10, Smad6 increased dramatically, Smad2, Smad3, and Smad4 remained elevated while Smad1 and Smad5 decreased in the fracture callus. Smad7 was expressed only in vascular endothelial cells. By day 28, when new bone had replaced the fracture callus, all the protein regulators decreased, approaching control levels. During fracture healing, the expression patterns of Smads1 and 5 were similar to that of BMPs-2 and 7 whereas the expression of Smads2 and 3 was parallel with that of TGF-β. The Smad family, associated with BMPs and TGF-β, may play an important role in the early stage of rat fracture healing.",
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TGF-β, BMPs, and their signal transducing mediators, Smads, in rat fracture healing. / Ohan, Mark P.; Weadock, Kevin S.; Dunn, Michael.

In: Journal of Biomedical Materials Research, Vol. 60, No. 3, 05.06.2002, p. 392-397.

Research output: Contribution to journalArticle

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AB - Smads are cytoplasmic signal transducers of transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs). Their relation to fracture healing is unknown. This study examined the temporal protein expression of Smads, together with TGF-β and BMPs, using immunohistochemistry in a rodent fracture model. Over-expression of TGF-β, BMPs-2, 4, and 7, common-mediator Smad (Smad4), and receptor-regulated Smads (Smads1, 2, 3, and 5) versus lower levels of inhibitory Smad (Smad6), were detected at day 3 in osteogenic cells in the thickened periosteum and bone marrow at the fracture sites. At day 10, Smad6 increased dramatically, Smad2, Smad3, and Smad4 remained elevated while Smad1 and Smad5 decreased in the fracture callus. Smad7 was expressed only in vascular endothelial cells. By day 28, when new bone had replaced the fracture callus, all the protein regulators decreased, approaching control levels. During fracture healing, the expression patterns of Smads1 and 5 were similar to that of BMPs-2 and 7 whereas the expression of Smads2 and 3 was parallel with that of TGF-β. The Smad family, associated with BMPs and TGF-β, may play an important role in the early stage of rat fracture healing.

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