TGF-beta, BMPS, and their signal transducing mediators, Smads, in rat fracture healing.
Smads are cytoplasmic signal transducers of transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMPs). Their relation to fracture healing is unknown. This study examined the temporal protein expression of Smads, together with TGF-beta and BMPs, using immunohistochemistry in a rodent fracture model. Over-expression of TGF-beta, 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-beta. The Smad family, associated with BMPs and TGF-beta, may play an important role in the early stage of rat fracture healing.
Yu
Yan
Y
Orthopaedic Research Laboratories, Division of Surgery, Prince of Wales Hospital, Faculty of Medicine, University of New South Wales, Sydney, NSW 2031, Australia.
Yang
Jia-Lin
JL
Chapman-Sheath
Philip J
PJ
Walsh
Williams R
WR
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D051785:Smad Proteins; D051898:Smad1 Protein; C497400:Smad1 protein, rat; D051902:Smad5 Protein; C497799:Smad5 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta