transforming-growth-factor-beta and Rib-Fractures

Ihh is a secreted protein expressed in chondrocytes in cartilaginous soft callus and thought to be involved in regulation of chondrogenic differentiation in fracture repair processes. However, gene expression and function of Ihh and its signaling molecules, Ptc and Smo, at the initial stage of fracture repair remain unknown. In the present study, we showed by RT-PCR of mouse rib fractures that the upregulation of Ihh mRNA occurred within hours after fracture, immediately followed by that of Ptc mRNA, and that both Ihh and Ptc mRNAs exhibited the time course similar to those of OP and OC mRNAs at the initial stage of fracture repair. The transcript level of Smo mRNA gradually increased within hours after fracture and was continuously maintained throughout the subsequent fracture repair processes. By in situ hybridization analysis, the transcripts of Ptc and Smo genes localized in bone marrow of unfractured ribs, and those of Ihh, Ptc, and Smo were expressed in the vicinity of the fracture site at 8 h after fracture. Furthermore, in adherent bone marrow cells in culture, mrIhh-N upregulated the gene expression of TGF-beta(1) as well as OPGL, a potent stimulator of osteoclastogenesis and osteoclast activity. These observations suggest that Ihh may play roles in the initial stage of fracture repair via TGF-beta(1) and OPGL.

Topics: Animals; Bone Marrow Cells; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Cell Adhesion; Cells, Cultured; Fracture Healing; Glycoproteins; Hedgehog Proteins; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Osteoprotegerin; Parathyroid Hormone-Related Protein; Patched Receptors; Patched-1 Receptor; Proteins; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Receptors, Tumor Necrosis Factor; Rib Fractures; RNA, Messenger; Signal Transduction; Smoothened Receptor; Trans-Activators; Transforming Growth Factor beta; Up-Regulation

To observe the effect of TGF-beta 1 in the regulation of fracture healing.. The expression of transforming growth factor-beta 1 (TGF-beta 1) in different period of fracture healing was investigated by immunohistochemistry.. It was found that the expression of TGF-beta 1 changed in different period. The cells in the cambial layer of the periostlum showed low or negative signal in the immediate injury response period. The osteoblasts differentiated from the periosteum cells stained strongly in the intramembranous ossification period, and the differentiated chondrocytes stained most strongly in the chondrogenesis period. The hypertrophic chondrocytes showed negative signal and the osteoblasts stained strongly in the endochondral ossification period. These results suggested that the expression of TGF-beta 1 was closely related to the proliferation and differentiation state of repair cells.. TGF-beta 1 is intimately involved in the control of fracture healing.

Topics: Animals; Fracture Healing; Rats; Rats, Wistar; Rib Fractures; Transforming Growth Factor beta