Bone morphogenetic proteins: from developmental signals to tissue regeneration

Šimić, Petra; Vukičević, Slobodan

doi:10.1038/sj.embor.7400943

Cited by 30 publications

(26 citation statements)

References 15 publications

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“…The roles of individual BMPs have been studied through the identification of mutated genes in classic mouse mutants and through conventional gene targeting approaches, gene disruption and overexpression of genes encoding BMPs, BMPRs and Smads. Collectively, these studies have confirmed that BMPs have important roles in the development of the skeleton, nervous system, eye, kidney, heart and primordial germ cells [36][37][38][39][40][41][42][43][44][45][46][47][48][49]. Bone healing in mammals is however restricted compared to more complex embryonic events like limb development that remains active following limb amputation in amphibians.…”

Section: Bmpsmentioning

confidence: 71%

“…BMP7 primarily stimulated the differentiation and mobility of cells outside the bone cavity originating from the periosteum and surrounding muscles to rebridge the fracture outside the bone defect, which later occupied the endosteal bone space. It has been well established that BMP2 and BMP7 turn muscles into bone via upregulating the inhibition of differentiation (Id) genes [45,[110][111][112], and in parallel promote the differentiation of pericytes and myoblasts into osteoblasts (Fig. 3) [113].…”

Section: Clinical Testing Of Bmp2 and -7 Revisedmentioning

confidence: 99%

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The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing

Vukičević

Oppermann

Verbanac

et al. 2013

International Orthopaedics (SICOT)

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105

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Purpose The purpose of this study was to revise the clinical use of commercial BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of action and efficacy of low BMP6 doses in a novel whole blood biocompatible device OSTEOGROW. Methods Complications from the clinical use of BMP2 and BMP7 have been systemically reviewed in light of their role in bone remodeling. BMP6 function has been assessed in Bmp6-/-mice by μCT and skeletal histology, and has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in rats and rabbits.Results Clinical use issues of BMP2 and BMP7 have been ascribed to the limited understanding of their role in bone remodeling at the time of device development for clinical trials. BMP2 and BMP7 in bone devices significantly promote bone resorption leading to osteolysis at the endosteal surfaces, while in parallel stimulating exuberant bone formation in surrounding tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6, applied in a biocompatible blood coagulum carrier, for stimulating differentiation of MSCs and accelerated healing of critical size bone defects in animals, without bone resorption and inflammation. BMP6 decreased the number of Mladenka Jurin contributed equally to this paper. S. Vukicevic (*) : J. Curak : J. Brkljacic : M. Pauk : I. Erjavec : I. Dumic-Cule : R. Novak : V. Kufner : T. Bordukalo Niksic :

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Section: Bmpsmentioning

confidence: 71%

Section: Clinical Testing Of Bmp2 and -7 Revisedmentioning

confidence: 99%

The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing

Vukičević

Oppermann

Verbanac

et al. 2013

International Orthopaedics (SICOT)

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105

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“…Recently, it was shown that TβRIII has also an important function as a suppressor of breast and prostate cancer progression [3,16]. The possibility of following the cancer progression by detection of TßRIII in plasma should be further examined, especially knowing the role of TGFβ-1 and related family members in the progression of tumour growth and metastasis [14]. TGF-β IG-H 3 adhesion protein in plasma may play an important role in the cell-collagen interactions and binding to type I, II and IV collagens and may have an important role in the endochondral bone formation.…”

Section: Discussionmentioning

confidence: 99%

Detection of bone and cartilage-related proteins in plasma of patients with a bone fracture using liquid chromatography–mass spectrometry

Grgurević

Maček

Đurđević³

et al. 2007

International Orthopaedics (SICO

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Following bone fracture, a large number of growth factors, cytokines, and their cognate receptors involved in the repair process are active at the fracture site. To determine whether they appear in patients' blood as candidate biomarkers for following the outcome of healing, we analysed the plasma of 25 patients with an acute bone fracture following affinity plasma purification, SDS gel electrophoresis and liquid chromatography -tandem mass spectrometry (LC-MS/ MS). Two hundred and thirteen nonredundant proteins were identified in the in-gel analysis of pooled plasma proteins. Gene ontology (GO) analysis indicated that a majority of detected proteins were of extracellular origin, whereas only a small number were of intracellular (cytosol and nucleus) origin. A significant proportion of detected proteins was involved in the cell growth and proliferation, transport and coagulation. Twelve proteins were potentially related to bone and cartilage metabolism, and several have not been previously identified in the plasma, including: TGF-β induced protein IG-H 3 , cartilage acidic protein 1, procollagen C proteinase enhancer protein and TGF-β receptor III.Résumé Après une fracture, un grand nombre de facteurs de croissance, cytokines et leurs récepteurs apparentés interviennent dans le processus de réparation des foyers de fracture. Nous avons analysé ces différents facteurs circulants chez 25 patients ayant présenté une fracture après purification du sang, électrophorèses, chromatographie et spectrographie de masse. 213 protéines ont été identifiées. L'analyse génétique de la majorité de ces protéines montre qu'elles sont d'origine extra cellulaires avec un très petit nombre de protéines intra cellulaires provenant notamment du noyau. Une proportion significative des protéines détectées intervient au niveau de la croissance, de la prolifération cellulaire et des phénomènes de coagulation. 12 protéines sont spécifiquement en rapport avec les métabolismes osseux et cartilagineux, plusieurs d'entre-elles n'avaient pas été préala-blement identifiées au niveau du plasma comme la TGF-β, la protéine IG-H3, la CAP 1, le procollagène de type C, le TGF-β récepteur III.

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“…125,126 The ligand-induced activation of BMP receptors exhibits intrinsic serine/threonine kinase activity that triggers the phosphorylation of R-smads. Smad2 and smad3 are phosphorylated by type I receptors of TGF-b and activin, whereas smad 1, smad5 and smad8 act downstream of the BMP type I receptors.…”

Section: Perspective: Anti-fibrosis Therapymentioning

confidence: 99%

Pathophysiology of the aging kidney and therapeutic interventions

2012

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Kidneys are among the organs affected by the aging process. Aging kidneys are characterized by progressive scarring and measurable declines in renal function. Deficiencies in renal function are associated with mortality in all populations. Therefore, if the kidneys age at an accelerated rate relative to the other organs in a particular individual, then slowing or reversing the kidney aging process may be a therapeutically useful strategy. In this review, we will discuss the physiology and pathogenesis of kidney aging and analyze potential therapeutic strategies for halting the aging process in the kidneys.

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Bone morphogenetic proteins: from developmental signals to tissue regeneration

Cited by 30 publications

References 15 publications

The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing

The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing

Detection of bone and cartilage-related proteins in plasma of patients with a bone fracture using liquid chromatography–mass spectrometry

Pathophysiology of the aging kidney and therapeutic interventions

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