Recombinant Transforming Growth Factor-β1 Induces Endochondral Bone in the Baboon and Synergizes with Recombinant Osteogenic Protein-1 (Bone Morphogenetic Protein-7) to Initiate Rapid Bone Formation

Ripamonti, Ugo; Duneas, Nicolaas; Heever, B. Van Den; Bosch, Carles; Crooks, Jean

doi:10.1359/jbmr.1997.12.10.1584

Cited by 151 publications

(181 citation statements)

References 46 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

350

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

350

241

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“…In the cranial periosteum of the rabbit, the amount of BMP-2 could be greatly reduced by combined use with prostaglandin E 1 (118). TGFb attenuated the stimulatory effect of rhBMP-2 in cultures of human bone marrow stromal cells (70), but stimulated OP-1-dependent bone induction in adult baboons in vivo (119).…”

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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“…11 An investigation of the profiles of type of chondroitins produced by hDFs cultured for 7 days showed greatest similarity with DBP for a combination of BMP-2 and TGF-b1 than by either alone. 6 Other investigators showed synergy of differentiation effects with combinations of BMP-2 and TGFb1 23 or of OP-1 and TGF-b1, 24 but did not make comparisons with demineralized bone.…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations of cDNA and amplification conditions were optimized for each gene product to reflect the exponential phase of amplification. One microliter of the cDNA solution was used in each PCR (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) cycles at 948C for 1 min, 55 or 608C for 1 min, and 728C for 2 min) with human gene specific primers: bigh3/TGFBI and ID3, 10 WNTs, 11 Cbfa1/Runx2 and Col1A1, 18 and SOX9. 19 …”

Section: Cell Cultures In Collagen Scaffoldsmentioning

confidence: 99%

Wnt pathway regulation by demineralized bone is approximated by both BMP‐2 and TGF‐β1 signaling

Zhou

Mizuno

Glowacki

2012

Journal Orthopaedic Research

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Allogeneic demineralized bone is used extensively as a clinical graft material because it has osteo/chondroinductive and osteoconductive properties. Demineralized bone powder (DBP) induces chondrogenic differentiation of human dermal fibroblasts (hDFs) in three-dimensional collagen cultures, but the initiating mechanisms have not been fully characterized nor has it been shown that bone morphogenetic proteins (BMPs) recapitulate DBP's effects on target cells. Among the many signaling pathways regulated in hDFs by DBP prior to in vitro chondrogenesis, there are changes in Wnts and their receptors that may contribute to DBP actions. This study tests the hypothesis that DBP modulation of Wnt signaling entails both BMP and TGF-b pathways. We compared the effects of DBP, TGF-b1, or BMP-2 on Wnt signaling components in hDFs by Wnt signaling macroarray, RT-PCR, in situ hybridization, and Western immunoblot analyses. Many effects of DBP on Wnt signaling components were not shared by BMP-2, and likewise DBP effects on Wnt genes and b-catenin only partially required the TGF-b pathway, as shown by selective inhibition of TGF-b/activin receptor-like kinase. The analyses revealed that 64% (16/25) of the Wnt signaling components regulated by DBP were regulated similarly by the sum of effects by BMP-2 and by TGF-b1. In conclusion, signaling mechanisms of inductive DBP in human dermal fibroblasts involve the modulation of multiple Wnt signals through both BMP and TGF-b pathways. ß

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Recombinant Transforming Growth Factor-β1 Induces Endochondral Bone in the Baboon and Synergizes with Recombinant Osteogenic Protein-1 (Bone Morphogenetic Protein-7) to Initiate Rapid Bone Formation

Abstract: Several members of the bone morphogenetic protein (BMP) and transforming growth factor-␤ (TGF-␤

Cited by 151 publications

References 46 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

Bone morphogenetic proteins in human bone regeneration

Wnt pathway regulation by demineralized bone is approximated by both BMP‐2 and TGF‐β1 signaling

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