Expression and distribution of transforming growth factor-β isoforms and their signaling receptors in growing human bone

Hörner, A.; Kemp, Paul R.; Summers, Charlotte; Bord, S.; Bishop, Nick; Kelsall, AW; Coleman, Nick; Compston, Juliet

doi:10.1016/s8756-3282(98)00080-5

Cited by 123 publications

(96 citation statements)

References 29 publications

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“…TGF␤1 has been shown to stimulate proliferation and collagen synthesis by osteoblasts and osteoblast precursors. [11][12][13] It also may act as a chemotactic agent in recruiting preosteoblasts to the site of bone injury. PDGF also stimulates mitogenesis of osteoblastic precursors.…”

Section: Discussionmentioning

confidence: 99%

Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation

Landesberg¹,

Roy²,

Glickman³

2000

Journal of Oral and Maxillofacial Surgery

353

241

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Purpose: This study compared two methods of preparing platelet-rich plasma (PRP) gel and the levels of PDGF and TGF␤ in each preparation. Materials and Methods:Platelet-rich plasma gel was prepared by centrifugation and clotted using the ITA gelling agent (Natrex Technologies Inc, Greenville, NC) or by the addition of thrombin and calcium chloride. The levels of platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF␤) generated by clot formation were assayed by enzyme-linked immunoassay (ELISA).Results: Both methods of preparation yielded PRP gel in less than 30 minutes. However, the ITA preparation did not require thrombin to achieve adequate gel formation. The levels of PDGF and TGF␤ were similar regardless of which method was used for initiation of clot formation. Conclusion:Use of ITA for gel preparation is equivalent to using calcium chloride and thrombin, without the need for special equipment and the risk of coagulopathy.Platelet-rich plasma (PRP) gel is derived from an autogenous preparation of concentrated platelets. PRP gel has numerous applications, particularly in the cardiac and neurosurgical areas. 1,2 Recently it has undergone a significant increase in use as an adhesive with cancellous bone particles in oral and maxillofacial surgery bone grafting procedures. 3,4 The traditional method of PRP preparation involves isolating platelets with a cell separator (Medtronics, Parker, CO), followed by gel formation using calcium chloride and bovine thrombin. This procedure has several disadvantages. The equipment necessary is expensive and is generally available only in an operating room or blood bank facility, making the use of PRP in a private office extremely difficult. Furthermore, the use of bovine thrombin has been associated with the development of antibodies to clotting factors V, XI, and thrombin, resulting in the risk of life-threatening coagulopathy. 1,2,5-7 We describe a new method to prepare PRP gel using a simplified armamentarium of equipment and supplies. This procedure can be used in an office setting and will yield an adequate amount of PRP gel for most minor bone grafting procedures. Additionally, this method uses an alternative to thrombin for gelling of the PRP, making it a safer preparation than that currently available.PRP is known to contain a number of growth factors/cytokines that may aid in the accelerated maturation of a bone graft. 4 Although platelet-derived growth factor (PDGF) and transforming growth factor-␤ (TGF␤) have been identified in PRP gel, the amounts have not been quantified. It is also unclear as to whether the method used to gel the PRP affects the amount of growth factors/cytokines released from the platelets. We therefore compared the levels of PDGF and TGF␤ generated from PRP prepared with the ITA gelling agent (Natrex Technologies Inc, Greenville, NC) and the thrombin/calcium chloride method.

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Section: Discussionmentioning

confidence: 99%

Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation

Landesberg¹,

Roy²,

Glickman³

2000

Journal of Oral and Maxillofacial Surgery

353

241

View full text Add to dashboard Cite

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“…TGF-s and TGFreceptors are expressed in developing and adult cartilage (Sandberg et al 1988, Pelton et al 1990, 1991, Horner et al 1998, Matsunaga et al 1999. Mice carrying null mutations of the gene encoding TGF-2 have skeletal abnormalities (Sanford et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Signaling cross-talk between IGF-binding protein-3 and transforming growth factor-β in mesenchymal chondroprogenitor cell growth

O'Rear

Longobardi

Torello

et al. 2005

Journal of Molecular Endocrinology

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Cartilage formation is driven by mesenchymal chondroprogenitor cells (MCCs) that proliferate and differentiate into chondrocytes. The molecular mechanisms by which growth factors regulate MCC fate are not well defined. Insulin-like growth factor binding protein-3 (IGFBP-3) has intrinsic bioactivity that is independent of IGF binding. We previously reported that IGFBP-3 has IGF-independent antiproliferative and apoptotic effects in MCCs, and requires STAT-1 activation to mediate its apoptotic effect. Transforming growth factor-(TGF-) is a key chondroinductive growth factor. The objective of the study is to define the interactions between IGFBP-3 and TGF-in MCC growth and their intracellular signaling pathways. We used the RCJ3·1C5·18 mesenchymal chondrogenic cells that without biochemical or oncogenic transformation progress in culture from MCCs to differentiated chondrocytes. Cell proliferation was assessed in MCCs treated with IGFBP-3 or transfected with IGFBP-3, in the presence or absence of TGF-. To demonstrate that IGFBP-3 effects were IGF-independent an IGFBP-3 analog that lacks IGF binding was used (GGG-IGFBP-3). To determine the functional roles of the TGF--mediated signaling and the STAT-1 pathway, cells were either stably transfected with a dominant negative TGF-type II receptor (MCC-DNT RII) or treated with a STAT-1 morpholino antisense oligonucleotide. We found that in MCCs, TGF-antagonized the antiproliferative effect of IGFBP-3. IGFBP-3 increased the cyclin-dependent kinase inhibitor p21 expression and this effect was abolished by TGF-. Furthermore, TGF-inhibited STAT-1 phosphorylation induced by IGFBP-3. Similarly to TGF-, STAT-1 antisense oligonucleotide inhibited the IGFBP-3 antiproliferative action. Although TGF-in MCC-DNT RII lacked Smad-mediated signaling, it persistently antagonized the IGFBP-3 antiproliferative action. However, TGF-even in MCC-DNT RII cells induced ERK1/2 phosphorylation, and treatment with MEK inhibitor, UO126, inhibited the antagonistic effects of TGF-on IGFBP-3. Furthermore, UO126 blocked the TGF-inhibition of STAT-1 phosphorylation induced by IGFBP-3. Collectively, these results demonstrate cross-talk between the IGFBP-3-dependent STAT-1 signaling and the TGF--dependent ERK pathway that regulates MCC proliferation.

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“…Transforming growth factor-␤ (TGF-␤) 1 is one of the most abundant growth factors in skeletal tissues (1) and, in mammals, comprises three isoforms, TGF-␤1, TGF-␤2, and TGF-␤3, all of which are expressed by bone cells (2) and interact with the known TGF-␤ type I-III receptors (betaglycan) (3). TGF-␤ plays a key role in osteoblast differentiation and bone development and remodeling.…”

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confidence: 99%

Transforming Growth Factor-β1 Regulation of Collagenase-3 Expression in Osteoblastic Cells by Cross-talk between the Smad and MAPK Signaling Pathways and Their Components, Smad2 and Runx2

Selvamurugan¹,

Kwok²,

Alliston

et al. 2004

Journal of Biological Chemistry

120

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Transforming growth factor-␤ (TGF-␤) plays a key role in osteoblast differentiation and bone development and remodeling. Collagenase-3 (matrix metalloproteinase-13) is expressed by osteoblasts and seems to be involved in osteoclastic bone resorption. Here, we show that TGF-␤1 stimulates collagenase-3 expression in the rat osteoblastic cell line UMR 106-01 and requires de novo protein synthesis. Dominant-negative Smad2/3 constructs indicated that Smad signaling is essential for TGF-␤1-stimulated collagenase-3 promoter activity. Inhibitors of the ERK1/2 and p38 MAPK pathways, but not the JNK pathway, reduced TGF-␤1-stimulated collagenase-3 expression, indicating that the p38 MAPK and ERK1/2 pathways are also required for TGF-␤1-stimulated collagenase-3 expression in UMR 106-01 cells. These inhibitors did not prevent nuclear localization of Smad proteins, but they inhibited Smad-mediated transcriptional activation. We have shown for the first time that Runx2 (a bone transcription factor and a potential substrate for the MAPK pathway) is phosphorylated in response to TGF-␤1 treatment in osteoblastic cells. Cotransfection of Smad2 and Runx2 constructs had a cooperative effect on TGF-␤1-stimulated collagenase-3 promoter activity in these cells. We further identified ligand-independent physical interaction between Smad2 and Runx2. Taken together, our results provide an important role for cross-talk between the Smad and MAPK pathways and their components in expression of collagenase-3 following TGF-␤1 treatment in UMR 106-01 cells.

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Expression and distribution of transforming growth factor-β isoforms and their signaling receptors in growing human bone

Cited by 123 publications

References 29 publications

Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation

Quantification of growth factor levels using a simplified method of platelet-rich plasma gel preparation

Signaling cross-talk between IGF-binding protein-3 and transforming growth factor-β in mesenchymal chondroprogenitor cell growth

Transforming Growth Factor-β1 Regulation of Collagenase-3 Expression in Osteoblastic Cells by Cross-talk between the Smad and MAPK Signaling Pathways and Their Components, Smad2 and Runx2

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