Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur (original) (raw)
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Journal of Bone and Mineral Research, 2009
Osteogenic protein-1 (OP-1, also called BMP-7) is a bone morphogenetic member of the TGF-P superfamily. In the present study, we examined the effect of recombinant human OP-1 on cartilage and bone formation in organ cultures of metatarsal long bones of mouse embryos and compared the OP-1 effects with those of human TGF-P, and porcine TGF-PI and P2. Cartilage formation was determined by measurement of longitudinal growth of whole bone rudiments during culture and by the incorporation of 35S04 into glycosaminoglycans. Mineralization was monitored by %a incorporation in the acid-soluble fraction and by measuring the length of the calcifying center of the rudiment. Toluidine blue-stained histologic sections were used for 'quantitative histomorphometric analysis. We found that OP-1 stimulated cartilage growth as determined by sulfate incorporation and that it increased remarkably the width of the long bones ends compared with controls. This effect was partly caused by differentiation of perichondrial cells into chondracytes, resulting in increased appositional growth. In contrast to OP-1, TGF-P, and P2 inhibited cartilage growth and reduced the length of whole bone rudiments compared with controls. In the ossifying center of the bone rudiments, both OP-1 and TGF-P inhibited cartilage hypertrophy, growth of the bone collar, and matrix mineralization. These data demonstrate that OP-1 and TGF-P exhibit opposite effects on cartilage growth but similar effects on osteogenesis in embryonic mouse long bone cultures. Since both OP-1 and TGF-P have been demonstrated in embryonic cartilage and bone, these results suggest that they act as autocrine or paracrine regulators of embryonic bone development. spine. Spine 17:S33-36. 45. Sauren YMHF, Mieremet RHP, Groot CG, Koerten HK, Scherft JP 1991 Polyethyleneimine as a contrast agent for ultrastructural
International Journal of Morphology, 2006
ISSA, M. J. P.; TIOSSI, R.; PITOL, D. L. & MELLO, S. A. S. TGF-ß and new bone formation. Int. J. Morphol., 24(3):399-405, 2006. SUMMARY: The aim of this work is to present, by a literature review, the principal characteristics of TGF-beta, in the regulation and new bone formation. ISSA, M. J. P.; TIOSSI, R.; PITOL, D. L. & MELLO, S. A. S. TGF-ß y neoformación ósea. Int. J. Morphol., 24(3):399-405, 2006.
Journal of Cellular Physiology, 1994
This study examines the mechanism by which TGF-P1, an important mediator of cell growth and differentiation, blocks the differentiation of normal rat diploid fetal osteoblasts in vitro. We have established that the inability for pre-osteoblasts to differentiate is associated with changes in the expression of cell growth, matrix forming, and bone related genes. These include histone, jun 6, c-fos, collagen,
The role of transforming growth factor-β on retarded osteoblastic differentiation in vitro
Life Sciences, 1999
Various matrix growth factors play important roles in the development and growth of cartilage and bone. Among them transforming growth factor-l3 superfamily and espedally bone morphogenetic proteins are known to be important factors, since they induce bone and cartilage formation in ectopic sites in viva We have previously shown that the human osteosarcoma cell line Saos-2 expresses molecules that iiq vivo induce new bone formation with asymmetric bone maturation. In this study we examined the role of Saos-Zconditioned medium in prolonged cultures of mesenchymal C&IflOT1/2 cells. The C&FIOT1/2 cells were cultured with Saos-2condirioned medium for 28 days. We show that Saos-2-treated CsI-I/10T1/2 cells performed retarded osteoblastic differentiation when compared to recombinant BMP2 and -4 induced differentiation. We further show that this retardation is due to excessive amounts of transforming growth factor-l3 in Saos-Zconditioned medium. Our results also suggest that this model can well be used to study additional cofactors involved in retarded osteogenesis.
2014
Several members o f the bone moirphogenetic protein and osteogenic protein (BMP/OP) and transforming growth factor-13 (TGF-J3) families are molecular regulators o f cartilage and bone regeneration, although their precise mode o f signal transduction and combined interactions are poorly understood. The presence of several molecular forms suggests multiple functions in vivo as well as synergistic interactions during both embryonic bone development and regeneration of cartilage and bone in postfoetal life. Heterotopic and orthotopic implantation of BMPs/OPs elicit the local differentiation o f new bone in a number o f animal models studied, whereas reports to date show that implantation o f TGF-Bs in heterotopic sites o f the rat results in fibrovascular tissue formation, without evidence of bone formation. Instead, TGF-Bs show limited osteo-chondrogenic activity only when applied orthotopically in some, and not all of the animal models studied. Here, data are presented that show for t...
2007
Distraction osteogenesis is a well established clinical treatment for limb length dicrepancy and skeletal deformities. Transforming growth factor beta 1 (TGF-b1) is a multifunctional peptide which controls proliferation and expression of cells specific to bone like chondrocytes, osteoblasts, osteoclasts including mesenchymal precursor cells. To decrease the external fixation time with increasing the strength of regenerate (newly formed bone after distraction) we tested the effect of locally applied transforming growth factor beta 1 on distraction osteogenesis. A total of 28 mature female white New zealand rabbits weighing 3,5 kg-4,5 kg were studied. 10 animals were belonging to biomechanical testing group (5 for the study and 5 for the control subgroups), and the others were to histology group. In biomechanical group after tibial ostetomy TGF-b1 was applied subperiosteally for 5 days just proximal to osteotomy site. Control group received only the solvent. Seven days after tibial osteotomy distraction was started at a rate of 0.25mm/12 hours for 3 weeks with a unilateral fixator. Rabbits were sacrified at the end of a consodilation period 8 week after tibial osteotomy. We assessed density of the elongation zone of rabbit tibial bones with the computed tomography. Then biomechanical parametres were assessed using the torsional testing using the material testing machine. In histology group rabbits were classified as control and study (rabbits that were given TGF-b1). Rabbits were sacrified at the end of first week, second week and fourth week also at the end of consolidation period 8 week after tibial osteotomy. Immunohistochemical and histologic parameters were examined. Biomechanical testing was applied as tortional testing. These values are used in determination of maximal loading, stiffness and energy absorbed during testing (brittlenes). The histomorphometric examination looked for the differences between the study and control groups in terms of bone formation pattern, bone quality and quantity. The immunohistochemical studies investigated the mechanism of TGF-b1, and it's presence in different cell types. The results of this study suggest that locally applied TGF-b1 improves the mineral density of distraction gap and load to failure(energy absorbed during testing). Though there is no significant histomorphometric difference between the study and control groups, there is an increased bone mineral density and an according maximum energy absorbance in the study group. This effect can be explained by the following mechanism: TGF-b1 exerts it's effect on two different receptor types (Type 1 and 2). Type 1 receptors are localized to bone matrix and type 2 receptors are localized to the intracellular space. The specific stains utilized in the current experiment are specific to type 2 receptors. They have been shown to be down-regulated by exogenous TGF-b1 injections. Most probably, type 1