Systemic administration of recombinant transforming growth factor beta 2 (rTGF-β2) stimulates parameters of cancellous bone formation in juvenile and adult rats

Rosen, David; Miller, Scott C.; DeLeon, E.; Thompson, Andrea Y.; Bentz, Hanne; Mathews, M. Claravon; Adams, Steven P.

doi:10.1016/8756-3282(94)90300-x

Cited by 71 publications

(44 citation statements)

References 24 publications

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“…The recombinant proteins of the TGF-␤ family have been administrated locally or systemically in animal models (25). To take advantage of this approach, we continuously infused recombinant follistatin for 11 d using mini pumps that were implanted subcutaneously into 10-d-old neonatal rats.…”

Section: Resultsmentioning

confidence: 99%

Expression of the TGF-β Family of Ligands Is Developmentally Regulated in Skeletal Muscle of Neonatal Rats

et al. 2006

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ABSTRACT:To dissect the possible role of the transforming growth factor-␤ (TGF-␤) family in the regulation of skeletal muscle growth during the early postnatal period, the protein abundances of the TGF-␤ family and their correlation with protein synthesis were determined in skeletal muscle of neonatal rats. To obtain direct evidence of the role of these growth factors in the regulation of protein synthesis, the TGF-␤ inhibitor, follistatin, was infused into 10-d-old rats for 11 d and protein synthesis and phosphorylation of S6 kinase 1 (S6K1) and ribosomal protein (rpS6) were measured. TGF-␤2 abundance and protein synthesis in muscle decreased with development and were positively correlated. The abundances of bone morphogenetic protein 2 (BMP-2), BMP-7, and myostatin increased with development and were negatively correlated with protein synthesis. The abundances of BMP-2 and BMP-7 were positively correlated with BMP receptor IA (BMP-RIA) abundance. Activin A abundance was positively correlated with follistatin abundance and activin receptor IIB (Act-RIIB) abundance. Infusion of follistatin increased muscle protein synthesis and S6K1 and rpS6 phosphorylation. The results provide indirect and direct evidence of TGF-␤ family involvement in the regulation of muscle protein synthesis during the neonatal period. I t is well recognized that, during the neonatal period, rates of growth and protein turnover are very high (1). Furthermore, a more rapid gain in protein mass occurs in skeletal muscle than in the body as a whole (2). This high rate of muscle protein deposition is largely driven by the high fractional rate of protein synthesis in skeletal muscle (3). Using animal models, we have demonstrated that the fractional rate of protein synthesis in skeletal muscle is very high immediately after birth, and about 50% of the decline in protein synthesis occurs during the first 3 wk of life (4).A number of studies have shown that skeletal muscle protein synthesis in growing animals is both acutely and chronically sensitive to hormonal stimuli (5). Our studies using neonatal pigs indicate that an enhanced sensitivity to insulin and IGF-I contributes to the high rate of skeletal muscle protein synthesis and muscle growth in neonates and this effect declines with development (6,7). Although the TGF-␤ family of ligands has also been implicated in the regulation of skeletal muscle growth in embryos and mature animals (8,9), the possible role of these growth factors in skeletal muscle growth during the neonatal period remains poorly understood.TGF-␤2, a positive regulator of skeletal muscle growth in vivo (10), regulates when and where myoblasts fuse to myotubes and is expressed at high levels on embryonic d 14, at lower levels by postnatal d 3, and at negligible levels in adult muscle (10). Follistatin, another positive regulator of skeletal muscle growth, has been shown to be essential for normal development (11). Mice with a null mutation of follistatin die soon after birth with a range of defects including insufficient musc...

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Section: Resultsmentioning

confidence: 99%

Expression of the TGF-β Family of Ligands Is Developmentally Regulated in Skeletal Muscle of Neonatal Rats

et al. 2006

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“…Another possibility dealing with FGF-2-enhanced endosteal bone formation is the activation of pre-existing osteoblasts mediated by cytokines produced by proliferating osteoprogenitor cells. Indeed, as reported earlier, FGF-2 stimulates cultured osteoblastic cells to produce type β transforming growth factor (TGF-β) [18], which stimulates expression of markers of osteoblast differentiation, such as alkaline phosphatase, type I collagen and osteonectin, in most in vitro studies [11] and increases endosteal bone formation in vivo [21].…”

Section: Discussionmentioning

confidence: 92%

Systemic Injection of FGF-2 Stimulates Endocortical Bone Modelling in SAMP6, a Murine Model of Low Turnover Osteopenia.

Nagai

Tsukuda

Yamasaki

et al. 1999

The Journal of Veterinary Medical Science

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ABSTRACT. The effects of systemically administered fibroblast growth factor-2 (FGF-2) at doses of 0.1 and 0.3 mg/kg/day for 7 days were investigated 5-week-old male SAMP6 mice, a model of low turnover osteopenia. The bone histomorphometry in the distal epiphyseal growth plate of the femur showed that 0.3 mg/kg/day of FGF-2 decreased the longitudinal growth rate and cartilage cell production rate and increased the growth plate width. Growth plate chondrocytes showed the features of defective endochondral ossification at the same dosage level. In the distal one third of the femur, the marrow trabecular area, endocortical mineral apposition rate and/or bone formation rate were increased in both the SAMP6 mice given 0.1 and 0.3 mg of FGF-2/kg/day. In this region, the endocortical osteoblasts were hypertrophied with some layers of overlying proliferated fibroblastic mesenchymal cells. The presence of small foci of bone formation within the layers of these mesenchymal cells indicates their osteogenic potential. On the other hand, the periosteal bone formation rate in the mid-shaft of the femur was depressed in the 0.3 mg/kg/day group. These results suggest that systemically administered FGF-2 may have the possibility to increase the peak bone mass in SAMP6 by stimulating the osteoprogenitor cells to proliferate and differentiate into osteoblasts and enhancing endocortical bone modelling. The higher dose of FGF-2, however, inhibited both endochondral and periosteal bone formation.-KEY EORDS: bone histomorphometry, bone modelling, osteoporosis, SAM.

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“…The anabolic effects of TGF-β on bone formation were demonstrated by injecting TGF-β1 or TGF-β2 under the periosteum [35][36][37] . In addition, systemic administration of TGF-β2 increased the rate of bone formation and mineral apposition 38) . Using implantation experiments into the rat femur bone defects, Ranieri et al 25) studied the influence of loading TGF-β2 to hydroxyapatite/tricalcium phosphate coated titanium implants on bone response, and reported that 10 μg rhTGF-β2 loading increased bone regeneration, but a lower dose was not effective.…”

Section: Discussionmentioning

confidence: 99%

Bone response of TGF-β2 immobilized titanium in a rat model

Suzuki

Hayakawa

Kawamoto³

et al. 2014

Dent. Mater. J.

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The present study aimed to immobilize TGF-β2 onto titanium implants by using a tresyl chloride-activation technique and to evaluate the bone response of TGF-β2 immobilized titanium (TGF-β2/Ti) implants in a rat femur defect model. XPS and FT-IR measurements identified the presence of TGF-β2 on titanium. Atomic force microscopy showed globular images of immobilized TGF-β2. The contact angle of TGF-β2/Ti against water significantly decreased compared with untreated titanium (Ti). There was no change of surface roughness after immobilization of TGF-β2. Ti and TGF-β2/Ti implants were inserted into rat femur defects. TGF-β2/Ti showed more bone formation by calcein labeling and histological observation. The measurements of bone to implant contact (BIC) and bone mass (BM) around the implants revealed that BIC and BM of TGF-β2/Ti implants were significantly higher than those of Ti at 4 weeks after the implantation. In conclusion, TGF-β2/Ti implant effectively enhances bone regeneration around implants.

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Systemic administration of recombinant transforming growth factor beta 2 (rTGF-β2) stimulates parameters of cancellous bone formation in juvenile and adult rats

Cited by 71 publications

References 24 publications

Expression of the TGF-β Family of Ligands Is Developmentally Regulated in Skeletal Muscle of Neonatal Rats

Expression of the TGF-β Family of Ligands Is Developmentally Regulated in Skeletal Muscle of Neonatal Rats

Systemic Injection of FGF-2 Stimulates Endocortical Bone Modelling in SAMP6, a Murine Model of Low Turnover Osteopenia.

Bone response of TGF-β2 immobilized titanium in a rat model

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