The use of recombinant human bone morphogenetic protein-2 for the treatment of a delayed union following femoral neck open-wedge osteotomy

Baltzer, A. W. A.; Ostapczuk, Martin; Stosch, Daniel; Granrath, M.

doi:10.4081/or.2012.e4

Cited by 8 publications

(4 citation statements)

References 17 publications

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“…Previous studies reported that the incidence rate of delayed union after fracture and non-union was approximately 5-10%, and treatment of this remains a big problem in the field of orthopedics (8)(9)(10). In the BMP family, BMP2 is the main signaling protein regulating bone formation (11)(12)(13). BMP2 could induce differentiation of pluripotent mesenchymal progenitor cells into osteoblast cells, promoting bone forma-tion of osteoblast cells.…”

Section: Discussionmentioning

confidence: 99%

Construction of human BMP2-IRES-HIF1αmu adenovirus expression vector and its expression in mesenchymal stem cells

Liu

Zhang

et al. 2012

Molecular Medicine Reports

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The present study aimed to construct a novel recombinant adenovirus expression vector Ad-BMP2-IRES-HIF1αmu that expresses human bone morphogenetic protein (BMP2) and mutant hypoxia-inducible factor 1α, and investigated its effects in promoting neogenesis of bone and angiogenesis. The recombinant adenovirus BMP2, HIF1αmu and pIRES2-EGFP expression vectors were constructed and transfected into HEK293A cells. The groups were divided into group A, transfection with Ad-BMP2-IRES-HIF1αmu; group B, transfection with Ad-HIF1αmu-IRES-hrGFP-1; group C, transfection with Ad-BMP2-IRES-hrGFP-1; group D, transfection with Ad-IRES-hrGFP-1; group E, not transfected. Adenovirus liquid was transferred into rabbit mesenchymal stem cells (MSCs) pretreated with dexamethasone at the best multiplicity of infection (MOI). The mRNA and protein expression of BMP2 and HIF1α were detected by RT-PCR and western blot analysis. Adenovirus was successfully packaged. The expression level of HIF1α mRNA in group A and B was markedly higher than that in groups C, D and E, showing a significant difference (P<0.01). There was a significant difference in the expression level of BMP2 mRNA between group A and C (P<0.05) and this was markedly higher than that in groups B, D and E (P<0.01). The protein expression level of HIF1α in group A and B was markedly higher than that in groups C, D and E (P<0.01). The protein expression level of BMP2 in group A and C was markedly higher than that in groups B, D and E (P<0.01). The human BMP2-IRES-HIF1αmu adenovirus expression vector was successfully constructed and the experimental groups formed bone and blood vessels prior to the positive and negative control groups.

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Section: Discussionmentioning

confidence: 99%

Construction of human BMP2-IRES-HIF1αmu adenovirus expression vector and its expression in mesenchymal stem cells

Liu

Zhang

et al. 2012

Molecular Medicine Reports

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“…Several factors that increase bone formation, such as VEGF, PDGF, and BMPs, are available for treatment. Among these, the osteogenic efficacy of BMPs has been reported in many studies (Baltzer et al 2012). We reported the osteogenic effect of recombinant human BMP-2 for delayed union in dogs (Kim et al 2012b).…”

Section: Discussionmentioning

confidence: 99%

Clinical application of bone forming peptide-1 for nonunion fracture healing in a dog with Cushing's disease: a case report

Kim¹,

Shim²,

Yoon³

et al. 2015

Vet. Med. - Czech

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ABSTRACT:A nine-year-old, female Shih Tzu dog was referred to Chonnam National University Veterinary Teaching Hospital with a non-weight bearing lameness, pain in the right forelimb, increased appetite, and dermatological changes. A complete transverse fracture of the right ulnar trochlear notch was detected on survey radiographs. Cushing's disease was diagnosed using the adrenocorticotropic hormone test. The fracture site was repaired using an intramedullary (IM) pin, a 2.0 miniplate and screws, and 1 mg of bone forming peptide-1 (BFP-1) was applied to the fracture site. Post-operative radiographs were performed immediately, and at two and 17 weeks after the first surgery. After the first surgery, the patient fell from the bed, and the IM pin was broken. Thus, a second surgery was performed, and the broken IM pin was removed. To stimulate bone healing, we applied Matrigel containing 3 mg of BFP-1 to the fracture site 20 weeks after the first surgery. A narrowed fracture gap was seen radiographically three weeks after the second surgery, and a hard callus was observed on the cranial fracture line at eight weeks. Bone mineral density at the fracture site increased at 16 weeks. Gradual fracture healing was observed on radiographs over the 35 week period following the second surgery.

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“…The results of immunohistochemistry in the current study support the findings of some experiments which showed that ESW treatment significantly upregulated the expression of BMP-2 in some musculoskeletal diseases. [34353637] Ras protein and BMP increased by the shock waves treatment were found to induce the differentiation of undifferentiated mesenchymal cell into cells capable of osteogenesis and promote the formation of bone and cartilage. [38] Meanwhile, the results of the present study showed roughly focused ESWT to be effective in the treatment of osteoporotic fractures by inhibiting bone resorption and increasing bone formation by enhancing OPG and BMP-2.…”

Section: Discussionmentioning

confidence: 99%

Effects of Roughly Focused Extracorporeal Shock Waves Therapy on the Expressions of Bone Morphogenetic Protein-2 and Osteoprotegerin in Osteoporotic Fracture in Rats

Huang

et al. 2016

Chinese Medical Journal

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Background:Roughly focused extracorporeal shock waves therapy (ESWT) is characterized by a wide focal area, a large therapy zone, easy positioning, and less pain during treatment. The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) in osteoporotic fractures in rats.Methods:Seventy-two female Sprague-Dawley (SD) rats, 3 months old, were divided into sham-operated group (n = 6) and an ovariectomized (OVX) group (n = 66). Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation. The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm2, 60 doses/min, and 2000 pact quantities. The contralateral right tibia was left untreated and served as a control. Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting analysis.Results:Bone mineral density (BMD) at the proximal tibia, femur, and L5 spine was significantly reduced after ovariectomy. BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group. Meanwhile, bilateral oophorectomy resulted in a lower trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-OVX animals. Three months after bilateral oophorectomy, BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs (P < 0.001). These data showed that the SD rats became a suitable model of osteoporosis, 3 months after they were OVX. Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group. Compared with the contralateral controls, decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT, followed by a later increase at 7 days, was indicated by real-time PCR and Western blotting analysis. The OPG messenger RNA (mRNA) expression levels peaked at 6 weeks after the shock wave treatment, paired with a much earlier (at 4 weeks) increase of BMP-2, and declined close to normal at 8 weeks.Conclusions:Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats. BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling.

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The use of recombinant human bone morphogenetic protein-2 for the treatment of a delayed union following femoral neck open-wedge osteotomy

Cited by 8 publications

References 17 publications

Construction of human BMP2-IRES-HIF1αmu adenovirus expression vector and its expression in mesenchymal stem cells

Construction of human BMP2-IRES-HIF1αmu adenovirus expression vector and its expression in mesenchymal stem cells

Clinical application of bone forming peptide-1 for nonunion fracture healing in a dog with Cushing's disease: a case report

Effects of Roughly Focused Extracorporeal Shock Waves Therapy on the Expressions of Bone Morphogenetic Protein-2 and Osteoprotegerin in Osteoporotic Fracture in Rats

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