Expression of neurotrophins and their receptors (TRK) during fracture healing

To clarify the roles of neurotrophins and their receptors in bone formation , expression of neurotrophins and their receptors (TRK) in a model of mouse fracture healing was investigated, A total of 120 male ICR mice were studi ed. The right eighth rib of 70 mice was fractured. For sham operation as a control, the right eighth rib of 50 mice was similarly exposed but not frac tured, Localization of TRKA, TRKB, and TRKC in a rectangular region of the rib together with surrounding soft tissues was investigated by immunostaini ng. Localizations of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) at the fracture callus were also i nvestigated by immunostaining, and their mitochondrial RNA (mRNA) expressio ns were investigated by reverse transcriptase-polymerase chain reaction (RT -PCR), As a result, we observed two types of neurotrophin receptors in the bone forming al ea: immunostaining by anti-TRK was observed in almost all b one forming cells, and staining with anti-TRKC was observed in osteoblast-l ike cells and hypertrophic chondrocytes, but no staining was observed with anti-TRKB. On the other hand, localization of NGF was observed in almost al l bone forming cells, localization of BDNF was observed in osteoblast-like cells, and localization of NT-3 was observed in osteoblast-like cells and h ypertrophic chondrocytes at the fracture callus. Expression levels of the m RNA of three neurotrophins in the fractured rib were increased during the p rocess of healing, especially those of NGF and NT-3, which peaked at 2 days after the fracture. The level of BDNF mRNA increased gradually over 8 days , These findings show that neurotrophins and their receptors were expressed in bone forming tells, and suggest that they are involved in the regulatio n of bone formation as an autocrine and paracrine factor in vivo. (Bone 26: 625-633; 2000) (C) 2000 by Elsevier Science Inc. All rights reserved.