Orthopaedic applications of osteogenic protein-1 (BMP-7)

Pećina, Marko; Giltaij, Lex R.; Vukičević, Slobodan

doi:10.1007/s002640100262

Cited by 70 publications

(48 citation statements)

References 37 publications

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“…Pharmacological intervention in fracture healing or bone repair is still limited to bone morphogenetic proteins (BMP2 and BMP7) [18,21]. The cost effectiveness, degree of clinical benefit and long-term safety of these therapies have not been fully delineated.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 receptors in bone formation

Thompson

Paralkar

2007

International Orthopaedics (SICO

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Prostaglandins, PGE 2 in particular, have diverse actions on various organs, including inflammation, bone healing, bone formation, embryo implantation, induction of labour and vasodilatation, among others. However, systemic side effects have limited their clinical utility. The pharmacological activities of PGE 2 are mediated through four G protein-coupled receptor subtypes, EP1-EP4. Recent studies have shown that EP2 and EP4 receptors play important roles in regulating bone formation and resorption. EP2 and EP4 receptor-selective agonists have been shown to stimulate local or systemic bone formation, augment bone mass and accelerate the healing of fractures or bone defects in animal models upon local or systemic administration, thus, potentially offering new therapeutic options for enhancing bone formation and bone repair in humans. This review will focus on the studies related to bone formation and bone healing in the EP receptor knockout (KO) mice and the EP2 or EP4 receptor-selective agonist treated animal models.Résumé Les prostaglandines en particulier la PGE 2 ont des actions relativement diverses sur différents organes, notamment en termes d'inflammation, de réparation osseuse, de régénération osseuse, d'implantation embryonnaire, d'induction du travail et de vasodilatation. Ces études ont montré que les récepteurs EP2 et EP4 avaient donc un rôle important dans la régulation de formation osseuse et dans sa résorption. On a pu démontrer que les récepteurs EP2 et EP4 stimulaient de façon locale ou systémique la formation osseuse, augmentaient la masse osseuse et accéléraient la guérison des fractures ou la réparation des défects osseux chez les animaux. Ceci nous offre un nouveau potentiel thérapeutique concernant l'amélioration de la régénération osseuse et la réparation des lésions osseuses chez l'homme. Cette revue permet de mettre en valeur les études relatives à la formation et à la cicatrisation osseuse avec le récepteur EP chez la souris et les récepteurs ajustés EP2, EP4 chez les animaux modèles.

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Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 receptors in bone formation

Thompson

Paralkar

2007

International Orthopaedics (SICO

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“…Despite new concepts in fracture treatment, long bone fractures are at risk of poor fracture healing with a rate of nonunion ranging from 10 to 30 % [1][2][3][4][5][6][7]. Detection of delayedor non-union at the earliest time point is of crucial importance for the implementation of early therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Is the expression of Transforming Growth Factor-Beta1 after fracture of long bones solely influenced by the healing process?

Kaiser

Thomas

Köttstorfer

et al. 2012

International Orthopaedics (SICOT)

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Purpose Circulating TGF-β1 levels were found to be a predictor of delayed bone healing and non-union. We therefore aimed to investigate some factors that can influence the expression of TGF-β1. The correlation between the expression of TGF-β1 and the different socio-demographic parameters was analysed. Methods Fifty-one patients with long bone fractures were included in the study and divided into different groups according to their age, gender, cigarette smoking status, diabetes mellitus and regular alcohol intake. TGF-β1 levels were analysed in patient's serum and different groups were retrospectively compared. Results Significantly lower TFG-β1 serum concentrations were observed in non-smokers compared to smokers at week 8 after surgery. Significantly higher concentrations were found in male patients compared to females at week 24. Younger patients had significantly higher concentrations at week 24 after surgery compared to older patients. Concentrations were significantly higher in patients without diabetes compared to those with diabetes at six weeks after surgery. Patients with chronic alcohol abuse had significantly higher concentrations compared to those patients without chronic alcohol abuse. Conclusion TGF-β1 serum concentrations vary depending upon smoking status, age, gender, diabetes mellitus and chronic alcohol abuse at different times and therefore do not seem to be a reliable predictive marker as a single-pointin-time measurement for fracture healing.

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“…Bone morphogenetic proteins (BMP) are potent local factors that have been shown to have specific functions during organogenesis and embryogenesis, regulate the differentiation of mesenchymal progenitor cells, and promote bone and cartilage formation in bone and cartilage defects, fracture repair, and periodontal diseases [3,5,11,[15][16][17]. BMPs are members of the transforming growth factor-β (TGF-β) superfamily and were first identified by their ability to induce ectopic bone formation in vivo [11].…”

Section: Introductionmentioning

confidence: 99%

BMP-6 exerts its osteoinductive effect through activation of IGF-I and EGF pathways

Grasser

Orlić

Borovečki

et al. 2007

International Orthopaedics (SICO

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We have recently shown that human recombinant BMP-6 (rhBMP-6), given systematically, can restore bone in animal models of osteoporosis. To further elucidate the underlying mechanisms of new bone formation following systemic application of BMPs, we conducted gene expression profiling experiments using bone samples of oophrectomised mice treated with BMP-6. Gene set enrichment analysis revealed enrichment of insulin-like growth factor-I and epidermal growth factor related pathways in animals treated with BMP-6. Significant upregulation of IGF-I and EGF expression in bones of BMP-6 treated mice was confirmed by quantitative PCR. To develop an in vitro model for evaluation of the effects of BMP-6 on cells of human origin, we cultured primary human osteoblasts. Treatment with rhBMP-6 accelerated cell differentiation as indicated by the formation of mineralised nodules by day 18 of culture versus 28-30 days in vehicle treated cultures. In addition, alkaline phosphatase gene expression and activity were dramatically increased upon BMP-6 treatment. Expression of IGF-I and EGF was upregulated in human osteoblast cells treated with BMP-6. These results collectively indicate that BMP-6 exerts its osteoinductive effect, at least in part, through IGF-I and EGF pathways, which can be observed both in a murine model of osteopenia and in human osteoblasts.Résumé Nous avons récemment pu mettre en évidence que la BMP-6 (rhBMP-6), administrée de façon systématique, pouvait améliorer la restauration du capital osseux de modèles animaux avec ostéoporose. Nous avons conduit une expérimentation utilisant des souris ovarieactomisées traitées par BMP-6. L'analyse a montré qu'il y avait un apport d'insulin like growth factor et d'épidermal growth factor chez les animaux traités par BMP-6. Pour développer un modèle in vitro nous avons étudié l'effet de la BMP-6 sur les cellules de type ostéoplasties d'origine humaine. Le traitement par BMP-6 accélère la différenciation cellulaire au 18ème jour alors que normalement cette différence est notée aux alentours du 28ème et 30ème jour. De plus, l'expression du gène de la phosphatase alkaline et l'activité sont augmentées par le traitement par la BMP-6, de même en ce qui concerne l'IGF-1 et l'EGF. Ces résultats nous permettent de penser que le BMP-6 a un effet ostéo conducteur notamment pour les pathologies intéressant IGF-1 et EGF. Nous avons observé ces effets dans un modèle animal avec ostéoplastie et sur les ostéoblastes humains.

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Orthopaedic applications of osteogenic protein-1 (BMP-7)

Cited by 70 publications

References 37 publications

Prostaglandin E2 receptors in bone formation

Prostaglandin E2 receptors in bone formation

Is the expression of Transforming Growth Factor-Beta1 after fracture of long bones solely influenced by the healing process?

BMP-6 exerts its osteoinductive effect through activation of IGF-I and EGF pathways

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