Biology of bone morphogenetic proteins

Martinović, Snježana; Šimić, Petra; Borovečki, Fran; Vukičević, Slobodan

doi:10.1007/978-3-0348-7857-9_3

Cited by 9 publications

(12 citation statements)

References 119 publications

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“…Unlike PTH, which circulates in serum, BMP-6 circulates when bone regenerates, like in patients with multiple bone fractures. 3 This excludes other BMPs as potential circulating candidates in the regeneration of the skeleton including osteoporosis. 3 BMP-6 exerts its effects on bone via promoting bone formation and reducing bone resorption thereby providing a distinct means to accumulate bone tissue mass.…”

Section: Discussionmentioning

confidence: 99%

“…3 This excludes other BMPs as potential circulating candidates in the regeneration of the skeleton including osteoporosis. 3 BMP-6 exerts its effects on bone via promoting bone formation and reducing bone resorption thereby providing a distinct means to accumulate bone tissue mass. No known therapeutic agent achieves both effects by in vivo systemic administration.…”

Section: Discussionmentioning

confidence: 99%

“…Three-dimensional reconstruction of bone was performed using the triangulation algorithm. The trabecular bone volume (BV, mm 3 ), trabecular number (Tb.N, 1/mm), trabecular thickness (Tb.Th, m), and trabecular separation (Tb.Sp, m), were directly measured on three-dimensional images using the method described by Hildebrand et al (26). The trabecular bone pattern factor and the structure model index were computed using software provided with the micro-CT machine (27,28).…”

Section: Mc3t3-e1 Preosteoblastic Cell Line and Cellmentioning

confidence: 99%

“…Inferior bone strength and increased bone fracture rate of bone in patients with osteoporosis might be associated with decreased osteoinductive and thus self-regenerative bone capacity eventually due to the lower content of growth and differentiation factors including bone morphogenetic proteins in the bone extracellular matrix (1)(2)(3)(4).…”

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confidence: 99%

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Systemically Administered Bone Morphogenetic Protein-6 Restores Bone in Aged Ovariectomized Rats by Increasing Bone Formation and Suppressing Bone Resorption

Šimić

Culej

Orlić

et al. 2006

Journal of Biological Chemistry

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Although recombinant human bone morphogenetic proteins (BMPs) are used locally for treating bone defects in humans, their systemic effect on bone augmentation has not been explored. We have previously demonstrated that demineralized bone (DB) from ovariectomized (OVX) rats cannot induce bone formation when implanted ectopically at the subcutaneous site. Here we showed in vitro that 17␤-estradiol (E 2 ) specifically induced expression of Bmp6 mRNA in MC3T3-E1 preosteoblastic cells and that bone extracts from OVX rats lack BMPs. Next we demonstrated that 125 I-BMP-6 administered systemically accumulated in the skeleton and also restored the osteoinductive capacity of ectopically implanted DB from OVX rats. BMP-6 applied systemically to aged OVX rats significantly increased bone volume and mechanical characteristics of both the trabecular and cortical bone, the osteoblast surface, serum osteocalcin and osteoprotegerin levels, and decreased the osteoclast surface, serum C-telopeptide, and interleukin-6. E 2 was significantly less effective, and was not synergistic with BMP-6. Animals that discontinued BMP-6 therapy maintained bone mineral density gains for another 12 weeks. BMP-6 increased in vivo the bone expression of Acvr-1, Bmpr1b, Smad5, alkaline phosphatase, and collagen type I and decreased expression of Bmp3 and BMP antagonists, chordin and cerberus. These results show, for the first time, that systemically administered BMP-6 restores the bone inductive capacity, microarchitecture, and quality of the skeleton in osteoporotic rats.Bone loss during aging and after menopause in women is known to result from an imbalance between bone formation and resorption leading to altered bone microarchitecture and excess bone fragility. Inferior bone strength and increased bone fracture rate of bone in patients with osteoporosis might be associated with decreased osteoinductive and thus self-regenerative bone capacity eventually due to the lower content of growth and differentiation factors including bone morphogenetic proteins in the bone extracellular matrix (1-4).Demineralized bone matrix (DBM) 2 induces de novo bone formation when implanted into the rat muscle (5). On the contrary, DBM from OVX animals implanted into both normal and OVX rats induces only fibrous tissues suggesting that its decreased bone inducing activity is due to abnormal composition of bone from OVX rats and not to the 17␤-estradiol (E 2 )-deficient microenvironment (1). Lack of specific signals needed for ectopic bone induction may, at least in part, explain diminished bone potency to heal fractures in osteoporotic patients (6,7). It has been demonstrated that fetal osteoblastic cell lines treated by E 2 specifically express Bmp6 mRNA, whereas gene transcripts of other members of the BMP family are unaffected (8). A functional relationship between E 2 and BMP-6 was further suggested by E 2 binding to the Bmp6 gene promotor (9) and by increased BMP-6 immunostaining in bone marrow of mice treated with E 2 (10).Although numerous studies have unequivoc...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Mc3t3-e1 Preosteoblastic Cell Line and Cellmentioning

confidence: 99%

mentioning

confidence: 99%

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Systemically Administered Bone Morphogenetic Protein-6 Restores Bone in Aged Ovariectomized Rats by Increasing Bone Formation and Suppressing Bone Resorption

Šimić

Culej

Orlić

et al. 2006

Journal of Biological Chemistry

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“…Bone morphogenetic proteins (BMPs) or osteogenic proteins (OPs) are growth and differentiation factors capable of initiating the recruitment, attachment, proliferation, and differentiation of mesenchymal cells, leading to new bone formation [11,20]. Extensive clinical and pre-clinical research has been undertaken to investigate the role of OP-1 (BMP-7) in bone and cartilage regeneration [14].…”

Section: Introductionmentioning

confidence: 99%

Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis

Bilić

Šimić

Jelić

et al. 2006

International Orthopaedics (SICOT)

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We randomly assigned 17 patients with scaphoid non-union at the proximal pole to three treatment groups: (1) autologous iliac graft (n=6), (2) autologous iliac graft + osteogenic protein-1 (OP-1; n=6), and (3) allogenic iliac graft + OP-1 (n=5). Radiographic, scintigraphic, and clinical assessments were performed throughout the follow-up period of 24 months. OP-1 improved the performance of both autologous and allogenic bone implants and reduced radiographic healing time to 4 weeks compared with 9 weeks in group 1. Helical CT scans and scintigraphy showed that in OP-1-treated patients sclerotic bone was replaced by well-vascularised bone. The addition of OP-1 to allogenic bone implant equalised the clinical outcome with the autologous graft procedure. Consequently the harvesting of autologous graft can be avoided.Résumé Nous avons réparti 17 malades avec une pseudarthrose du pôle proximal du scaphoide en trois groupes aléatoires de traitement: (1) greffe autologue iliaque (n=6), (2) greffe autologue iliaque + protéine osteogenique-1 (OP-1; n=6), et (3) greffe allogène iliaque + OP-1 (n=5). L'estimation radiographique, scintigraphique et clinique a été exécutée pendant une période de suivi de 24 mois. L'OP-1 a amélioré la performance des autogreffes et des allogreffes osseuses et a réduit le temps curatif radiographique à 4 semaines, comparé à 9 semaines dans le groupe traité uniquement avec de l'os autologues. Chez les malades traités avec l'OP-1, la tomodensitométrie hélicoïdale et la scintigraphie ont montré que l'os scléreux était remplacé par de l'os bien vascularisé. L'addition d'OP-1 à la greffe allogène a égalisé le résultat clinique avec la procédure de greffe autologue et a permis de supprimer le temps de prise de greffe.

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Acid‐insoluble human dentin as carrier material for recombinant human BMP‐2

Murata

Sato

Hino

et al. 2011

J Biomedical Materials Res

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The aim of this study is to estimate the increase of bone-inductive potency by human demineralized dentin matrix (DDM) with recombinant human bone morphogenetic protein-2 (BMP-2). Human teeth were crushed, completely demineralized in 0.6M HCl, and freeze-dried. The tooth-derived material is called DDM. The shape of DDM was a particle type and its size varied from 0.4 to 0.8 mm. The BMP-2 dose-dependent study in the rat subcutaneous tissues demonstrated that the volume of induced bone and marrow increased at a dose-dependent manner. The time-course study of bone induction by the BMP-2 (5.0 μg)/DDM (70 mg) was estimated histologically and biochemically. Histological findings showed that the BMP-2/DDM increased bone and marrow sequentially between the DDM particles. Calcium content in the BMP-2/DDM-induced tissue was compatible to the histological findings. ALP activity in the BMP-2/DDM showed a maximal value at 1 week and gradually decreased. The morphometric analysis demonstrated that the BMP-2/DDM showed 66.9%, 79.0% in the volume of bone and marrow, and 32.4%, 21.0% in that of DDM at 8, 32 weeks, respectively. We confirmed that BMP-2 significantly accelerated bone formation in the acid-insoluble human-dentin carriers. These results indicate that human DDM should be an effective carrier for delivering BMP-2 and superior scaffold for bone-forming cells.

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Biology of bone morphogenetic proteins

Cited by 9 publications

References 119 publications

Systemically Administered Bone Morphogenetic Protein-6 Restores Bone in Aged Ovariectomized Rats by Increasing Bone Formation and Suppressing Bone Resorption

Systemically Administered Bone Morphogenetic Protein-6 Restores Bone in Aged Ovariectomized Rats by Increasing Bone Formation and Suppressing Bone Resorption

Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis

Acid‐insoluble human dentin as carrier material for recombinant human BMP‐2

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