"In closed long bone fracture, where the fracture is more likely unstable and endochondral ossification plays very important roles in its healing, FGFs can stimulate the expansion of cartilaginous callus, thus may have no or even harmful effects on the fracture healing. However, in osteotomy or stabilized fractures where the cartilaginous callus formation is very limited or absent, FGF can stimulate the proliferation of MSCs and osteoblasts, promote osteoblastic differentiation, and can lead to accelerated bone regeneration and better quality of the healed fracture (Nakajima et al., 2007, 2001b). There are 22 FGFs found so far; however, majority of them have not been studied carefully for their potential roles in fracture healing or bone regeneration. "
[Show abstract][Hide abstract] ABSTRACT: Fibroblast growth factor (FGF)/FGF (FGFR) signaling is an important pathway involved in skeletal development. Missense mutations in FGFs and FGFRs were found clinically to cause multiple congenital skeleton diseases including chondrodysplasia, craniosynostosis, syndromes with dysregulated phosphate metabolism. FGFs/FGFRs also have crucial roles in bone fracture repair and bone regeneration. Understanding the molecular mechanisms for the role of FGFs/FGFRs in the regulation of skeletal development, genetic skeletal diseases, and fracture healing will ultimately lead to better treatment of skeleton diseases caused by mutations of FGFs/FGFRs and fracture. This review summarizes the major findings on the role of FGF signaling in skeletal development, genetic skeletal diseases and bone healing, and discusses issues that remain to be resolved in applying FGF signaling-related measures to promote bone healing. This review has also provided a perspective view on future work for exploring the roles and action mechanisms of FGF signaling in skeletal development, genetic skeletal diseases, and fracture healing.
"MLV-based retroviral FGF-2 vectors were also tested for enhancement of fracture repair. FGF-2 has been proposed to function through cell proliferation, and recombinant FGF therapy had demonstrated increased callus size (Nakajima et al., 2001). FGF-2 gene therapy stimulated proliferation of periosteal and adjacent cells of the soft callus but did not lead to the development of hard callus or accelerate bony bridging (unpublished data). "
"However, due to the lack of mechanical testing, the equivalent union rate does not necessarily mean that quality of osseous healing is the same in the DM and control groups. We have previously shown that basic FGF-injected fracture calluses exhibited a lower bone union rate compared to controls due to enhanced cartilage formation  . "
[Show abstract][Hide abstract] ABSTRACT: Most studies have focused on the association between diabetes mellitus (DM) and impaired osseous healing, but there is also evidence that diabetes impairs cartilage formation during fracture healing. To investigate the molecular mechanisms by which diabetes affects endochondral ossification, experiments were performed in a model of rat closed fracture healing complicated with diabetes. Diabetic rats were created by a single intravenous injection of streptozotocin (STZ), while controls were treated with vehicle alone. Fractures were made 2 weeks after STZ injection. Animals were killed at 4, 7, 10, 14, 21, 28 and 42 days following fracture, and samples were subject to radiographic, histological and molecular analyses. In the DM group, a significantly smaller cartilaginous callus was formed compared with controls throughout healing, with the cartilage area being reduced rapidly after day 14. When the bone union rate was evaluated radiographically on day 28, DM calluses exhibited a lower rate than controls. However, when evaluated on day 42, both groups showed an equivalent union rate. Cellular proliferation of chondroprogenitor cells and proliferating chondrocytes in soft calluses of the DM group was significantly reduced during early stages of healing (days 4 and 7), but no longer reduced thereafter. Moreover, expression levels of collagen type II, type X and osteopontin (OPN) were constantly low in the DM group. These results show the molecular basis for diminished cartilage formation and delayed union in fracture healing of the STZ-induced diabetic rats.
Bone 09/2008; 43(5):832-9. DOI:10.1016/j.bone.2008.07.246 · 3.97 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.