Basic fibroblast growth factor and bone induction in rats

Wang, Jian‐Sheng; Aspenberg, Per

doi:10.3109/17453679308993692

Cited by 61 publications

(33 citation statements)

References 11 publications

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“…Local factors that have been shown to act synergistically with BMP are basic fibroblast growth factor (bFGF), prostaglandins and TGFb. bFGF has shown synergistic effects with BMP-2 in rat marrow cell cultures (116,117), but high doses of bFGF caused a profound inhibitory effect in vivo (117). In the cranial periosteum of the rabbit, the amount of BMP-2 could be greatly reduced by combined use with prostaglandin E 1 (118).…”

Section: Hormones and Growth Factors Affecting Bmp Activitymentioning

confidence: 99%

Bone morphogenetic proteins in human bone regeneration

Groeneveld

Burgér

2000

European Journal of Endocrinology

358

217

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Recently, the first clinical reports on bone regeneration by two recombinant human bone morphogenetic proteins (rhBMPs), BMP-2 and BMP-7 (also named osteogenic protein-1, OP-1) have been published (1-4) . Although both BMPs were able to support bone regeneration, a significant variation in individual response was observed with both proteins. Animal studies and laboratory experiments reveal a number of conditions that influence the osteoinductivity of BMP, such as BMP concentration, carrier properties and influence of local and systemic growth factors and hormones. In this paper, these studies and the clinical reports are reviewed, and the conditions that modulate the BMP-dependent osteoinduction are discussed. The information may provide clues as to how the performance of recombinant human BMP as bone-graft substitute in humans can be improved. European Journal of Endocrinology 142 9-21 BMP and demineralized bone matrixThe history of bone morphogenetic proteins (BMPs) began with the observation that demineralized bone matrix (DBM) is able to induce ectopic bone formation in subcutaneous and intramuscular pockets in rodents (5, 6). This bone induction process has been studied extensively (7-13). Histological and biochemical analyses showed that cartilage appears 5-10 days after implantation of active DBM (8). This cartilage mineralizes by day 7-14 and is subsequently replaced by bone (7-9). After 21 days, haematopoietic bone marrow formation can be observed (12). These cellular events observed after DBM implantation mimic embryonic bone development and normal fracture repair (11). As DBM-related bone formation was observed to occur at ectopic sites, it was assumed that pluripotent mesenchymal cells are attracted to the site of implantation. Isolation of the bone-inducing substance revealed that certain proteins were responsible, which were termed bone morphogenetic proteins (BMPs) or osteogenetic proteins (OPs).The use of DBM in treating bone defects has proven beneficial for bone regeneration both in animals and in humans (14-17). DBM has become widely accepted as a bone-graft substitute in clinical practice (18-22), but its bone inductive capacity has been questioned (23, 24). In several studies, including our own, histology revealed that new bone was generated by osteoconduction rather than osteoinduction (25-27) -that is, bone regeneration occurred by growth of existing host bone on the DBM granules, which acted as a scaffold, rather than by de novo differentiation of bone, independent of pre-existing bone. Lack of inductive properties of DBM may be related to the procedures of production of commercially available DBM, as preservation of osteoinductive activity can be affected by the processing (28-30) or sterilization procedures (31). It is also possible that DBM of human origin, which is preferred for use in clinical practice, is less osteoinductive than DBM derived from animals, which is commonly used in animal studies. Several studies show that DBM from long-lived species such as baboon and human...

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Section: Hormones and Growth Factors Affecting Bmp Activitymentioning

confidence: 99%

Bone morphogenetic proteins in human bone regeneration

Groeneveld

Burgér

2000

European Journal of Endocrinology

358

217

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“…We have recently demonstrated that a single injection at fracture sites facilitates fracture healing [12]. Aspenberg and his colleagues have reported that a local application of bFGF increased bone yield in implanted demineralised bone matrix [25]. Using young and old rats, two separate groups have shown that daily systemic administration of bFGF caused increased endosteal bone formation [14,17], and these effects were seen as early as 1 to 3 weeks whether the injection was either local or systematic.…”

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confidence: 99%

Stimulation of bone formation by intraosseous injection of basic fibroblast growth factor in ovariectomised rats

Nakamura

Kurokawa

Aoyama

et al. 1998

International Orthopaedics

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The effect on intraosseous bone formation of a single local injection of recombinant human basic fibroblast growth factor into trabecular bones was examined in ovariectomised osteoporotic rats. Fibroblast growth factor (400 micrograms), or the vehicle alone, was injected into the ilium at 16 weeks after ovariectomy or a simulated operation. Bone mineral density in the ovariectomised rats increased to a level similar to the latter at 2 weeks and reached a maximum at 8 weeks. After 8 weeks, BMD decreased slowly and the value at 24 weeks was still higher than that in the ovariectomised rats. Fibroblast growth factor stimulated osteoid formation in the first 2 weeks, bone volume reaching a peak at 8 weeks. From 8 to 12 weeks, bone resorption increased, resulting in decreases in bone volume to the levels of the group with simulated operations at 24 weeks. Structural analysis at 8 and 24 weeks showed that ovariectomy decreased the continuity of trabeculae and the injection of fibroblast growth factor restored it to levels higher than, or equal to, those who had the simulated operation. The present study demonstrated that intraosseous fibroblast growth factor given to ovariectomised rats restored bone volume and quality to the levels of the rats who had a simulated operation only.

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“…19 Accordingly, it was anticipated that the 10 g rhFGF-2 dose might inhibit osteogenesis. These authors concluded that the inhibition they observed resulted from an effect on mature osteoblasts, which were present in increasing numbers as the BHC filled with bone.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor-2 alters the effect of eroding polylactide-polyglycolide on osteogenesis in the bone chamber

Winet

Bao

1998

J. Biomed. Mater. Res.

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The effects of recombinant human fibroblast growth factor-2 (rhFGF-2) in the presence of eroding 50:50 poly(DL-lactide-co-glycolide) (PDLLG) on acute bone healing were studied in the optical bone chamber (BCI). BCIs were loaded with disks of PDLLG surrounded by one of four rhFGF-2 doses. Fifty-two female rabbit right tibias were implanted. Commencing the third week post implantation (W3) healing in the BCI compartment was observed weekly, using intravital microscopy, until W8. The doses were: unloaded, loaded with polymer only, and polymer plus 0.5, 1.0, and 10 microg rhFGF-2. Videotaped and photographed bone images were measured and analyzed using a frame-grabber digitizing system. Comparison with controls revealed that ossification rates were significantly above normal in rabbits loaded with polymer plus any of the rhFGF-2 doses. Comparison with polymer-only BCIs showed that PDLLG plus any of the three rhFGF-2 doses was linked with ossification rates significantly higher than baseline. The results indicated that FGF-2 in the dose range studied effectively can overcome the retarding effects of eroding polymer on ossification that has been reported by this laboratory. Interpretation of the retarding effects of the polymer disks, although consistent with previously studied washer-shaped devices of the same material, was complicated by a difference in erosion rate. This result supports the notion that erodible device geometry is a major factor in determining biocompatibility and must be considered in the design of carriers. Accordingly, programming of dose specificity for delivering a given polypeptide cytokine to a given host site must allow for the inhibitory effects of an eroding carrier and the influence of device geometry on these effects and erosion.

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Basic fibroblast growth factor and bone induction in rats

Cited by 61 publications

References 11 publications

Bone morphogenetic proteins in human bone regeneration

Bone morphogenetic proteins in human bone regeneration

Stimulation of bone formation by intraosseous injection of basic fibroblast growth factor in ovariectomised rats

Fibroblast growth factor-2 alters the effect of eroding polylactide-polyglycolide on osteogenesis in the bone chamber

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