Injecting Fibroblast Growth Factor FGF Into Fracture Sites From Distraction

Me: These types of studies are really the best type for us to see how they would effect the bones. From the 1st study, we see that from just adding 1 microgram of aFGF either every other day or every day we can get larger callus size, greater collagen content, more DNAm and also soft cartilagous callus. The calluses for the aFGF injected are bigger for at least 4 weeks until it was taken over by trabecular bone. However there was evidence from the histological testing that the mRNA expression for certain types of procollagen was lower.

From study three, we have just one injection of 100 microgram of basic FGF (bFGF) which increases the Collagen Type X and Type II mRNA expression (in hypertrophic and proliferative chondroctyes respectively) and increase the proliferation of chondroprogenitor cells in fracture callus, and thus contributes to the formation of a larger cartilage. This does not cause the ossification and maturation of the chondrocytes though. The healing process has not been decreased. In terms of height increase, this is a fascinating growth factor because it does not cause the ossification to overcome the new chondrocytes too quickly. Since maturation and ossification is the irriversible proess hypertrophic chondrocytes turn into the eventual bone, what we should be doing is maximizing the number of chondrocytes but also delaying the time of maturation. 

From study two, we have the experiment repeated with one injection of 100 microgram of bFGF encapsulated in 200 microliter of fibrin gel. The results and evaluated parameters of the bone union rate, bone mineral density (BMD), and mechanical properties (strength and stiffness) of the callus was no different between the control group and the FGF injected group. the mRNA expression was also not changed much between the two groups. Again, the author states that the FGF makes the callus from the distraction larger but the healing process is not accelerated. 

From PubMed study link HERE

J Orthop Res. 1990 May;8(3):364-71.

Acidic fibroblast growth factor (aFGF) injection stimulates cartilage enlargement and inhibits cartilage gene expression in rat fracture healing.

Jingushi S, Heydemann A, Kana SK, Macey LR, Bolander ME.

Source

Orthopaedic Research Unit, NIAMS, NIH, Bethesda, MD 20892.

Abstract

The effect of the administration of acidic fibroblast growth factor (aFGF) on normal fracture healing was examined in a rat fracture model. One microgram of aFGF was injected into the fracture site between the first and the ninth day after fracture either every other day or every day. aFGF-injected calluses were significantly larger than control calluses, although this does not imply an increased mechanical strength of the callus. Histology showed a marked increase in the size of the cartilaginous soft callus. Total DNA and collagen content in the cartilaginous portion of the aFGF-injected calluses were greater than those of controls, although the collagen content/DNA content ratio was not different between the aFGF-injected and control calluses. Fracture calluses injected with aFGF remained larger than controls until 4 weeks after fracture. The enlarged cartilaginous portion of the aFGF-injected calluses seen at 10 days after fracture was replaced by trabecular bone at 3 and 4 weeks. Northern blot analysis of total cellular RNA extracted separately from the cartilaginous soft callus and the bony hard callus showed decreased expression of type II procollagen and proteoglycan core protein mRNA in the aFGF-injected calluses when compared with controls. A slight decrease in types I and III procollagen mRNA expression was also observed. We concluded that aFGF injections induced cartilage enlargement and decreased mRNA expression for type II procollagen and proteoglycan core protein.

PMID:  2324855     [PubMed – indexed for MEDLINE]

From PubMed study link HERE 

Calcif Tissue Int. 2007 Aug;81(2):132-8. Epub 2007 Jul 19.

Effects of a single percutaneous injection of basic fibroblast growth factor on the healing of a closed femoral shaft fracture in the rat.

Nakajima F, Nakajima A, Ogasawara A, Moriya H, Yamazaki M.

Source

Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.

Abstract

Recently, bioactive agents to stimulate bone formation have been available in the orthopedic field. We have shown previously that a single, local injection of basic fibroblast growth factor (bFGF) contributes to the formation of a larger cartilage (soft callus) but does not promote replacement of the cartilage by osseous tissue during experimental closed femoral fracture healing. Aiming at a clinical application, the present study was undertaken to clarify the effects of locally injected bFGF on bone (hard callus) formation and the mechanical properties of the callus in closed fracture healing in rats. Immediately after fracture, a carrier (200 muL of fibrin gel) containing 100 mug of bFGF or carrier alone was applied to the fracture site. At days 42 and 56 postfracture, the bone union rate, bone mineral density (BMD), and mechanical properties (strength and stiffness) of the callus were evaluated. Unexpectedly, with the exception of reduced stiffness in the FGF-injected callus at day 56, none of these parameters showed a significant difference between the control and the FGF-injected groups. Furthermore, the temporal expression pattern of OPN mRNA during healing was very similar between groups. We conclude that, in the healing of closed fractures of long bones, administration of bFGF forms a larger callus but does not necessarily accelerate the healing process.

PMID:   17638037    [PubMed – indexed for MEDLINE]

From PubMed study link HERE

J Orthop Res. 2001 Sep;19(5):935-44.

Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor.

Nakajima F, Ogasawara A, Goto K, Moriya H, Ninomiya Y, Einhorn TA, Yamazaki M.

Source

Department of Orthopaedic Surgery, Chiba University School of Medicine, Japan.

Abstract

Chondrogenesis is an essential component of endochondral fracture healing, though the molecular and cellular events by which it is regulated have not been fully elucidated. In this study, we used a rat model of closed fracture healing to determine the spatial and temporal expression of genes for cartilage-specific collagens. Furthermore, to determine the effects of basic fibroblast growth factor (bFGF) on chondrogenesis in fracture healing, we injected 100 microg recombinant human bFGF into the fracture site immediately after fracture. In normal calluses, pro-alpha1(II) collagen mRNA (COL2A1) was detected in proliferative chondrocytes beginning on day 4 after the fracture, and pro-alpha1(X) collagen mRNA (COL10A1) in hypertrophic chondrocytes beginning on day 7. In FGF-injected calluses, the cartilage enlarged in size significantly. On day 14, both COL2A1- and COL10A1-expressing cells were more widely distributed, and the amounts of COL2A1 and COL10A1 mRNAs were both approximately 2-fold increased when compared with uninjected fractures. Temporal patterns of expression for these genes were, however, identical to those found in normal calluses. The number of proliferating cell nuclear antigen-positive cells was increased in the non-cartilaginous area in the bFGF-injected calluses by day 4. The present molecular analyses demonstrate that a single injection of bFGF enhances the proliferation of chondroprogenitor cells in fracture callus, and thus contributes to the formation of a larger cartilage. However, maturation of chondrocytes and replacement of the cartilage by osseous tissue are not enhanced by exogenous bFGF, and this results in the prolonged cartilaginous callus phase. We conclude that, in the healing of closed fractures of long bones, exogenous bFGF has a capacity to enlarge the cartilaginous calluses, but not to induce more rapid healing.

PMID:  11562144      [PubMed – indexed for MEDLINE]

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