• Journal of Periodontal and Implant Science
• /
• v.26 no.1
• /
• pp.68-79
• /
• 1996

To investigate the efficiency of a fibrous collagen membrane(FCM) composed of bovine skin type I atelocollagen as a carrier for BMP, partially purified bovine BMP/FCM($0.3mg/10{\times}5{\times}1mm$) composites were implanted into the dorsal subcutaneous tissue of rats. FCM alone was also implanted as a control. The implants were harvested at 1, 2, 3, and 10 weeks after implantation, then prepared for routine light microscopic observation. The FCM alone did not induce osteogenesis and revealed no specific foreign body reaction nor was there any definite resorptive evidence for 10 weeks after implantation, while the BMP/FCM composites induced favorable bone formation in a process that resembled an endochondral and direct ossification mode. At 10 weeks, the well formed bone confined to embedded collagen fibers revealed hematopoietic marrow between bony trabeculae without evidence of resorptive or degenerative changes . These findings support the suggestion that BMP may induce undifferentiated mesenchymal cells into either chondroblasts or osteoblasts or both independantly according to the chemico- physical characteristics of the carrier, which develops the endochondral and/or direct bone formation process, and suggest that the FCM may be a favorable carrier for BMP.

• Journal of Periodontal and Implant Science
• /
• v.36 no.3
• /
• pp.627-637
• /
• 2006

이 연구는 rh BMP-7-immobilized substrates에 대한 백서 태자 두개관 세포의 반응을 석회화 결절 측정, 알카리 효소 분석, 역전사 중합반응 및 단백질 분석등으로 평가하여 다음과 같은 결과를 얻었다. 1. 배양 14일 째, 석회화 결절 형성율을 측정한 결과, rh BMP-7-immobilized substrates에서 대조군과 비교하여 더 많은 석회화 결절을 형성하였다. 2. 배양 7일에 염기성 인산 분해효소 활성도는 rh BMP-7-immobilized substrates에서 대조군에 비해 효소 활성도가 유의하게 높았다. 3. 역전사 중합반응의 결과에서 BSP 와 OCN 유전자 발현은 대조군보다 더 현저하였다. 4. 단백질 분석에서 rh BMP-7-immobilized substrates와 대조군 모두 Smad 1,5,8 단백질의 인산화를 활성화시키지 못했다. 이상의 결과 rh BMP-7-immobilized substrates는 백서 태자 두개관세포가 조골세포로의 분화와 석회화를 유도하며 따라서 rh BMP-7-immobilized substrates는 임프란트 주변의 골 형성에 유용하리라 사료된다.

• BMB Reports
• /
• v.49 no.3
• /
• pp.179-184
• /
• 2016

Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/β-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/β-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering.

• International Journal of Oral Biology
• /
• v.49 no.2
• /
• pp.48-52
• /
• 2024

This study explores the histological features and Bmp4 expression patterns in the replaced tooth germ of Xenopus laevis. Tooth germ formation starts from the dental placode through epithelial-mesenchymal interactions, involving various signaling pathways such as Fgf, Shh, Bmp, and Wnt. In mice, Bmp4 expression in the dental placode inhibits Pax9 expression in the dental mesenchyme. Although absent in the presumptive dental lamina of birds and toothless mammals, Bmp4 remains conserved in reptiles and fish owing to gene duplication. However, its expression in amphibian tooth germs is poorly understood. Three-month-old X. laevis were employed in this study. Initially, samples underwent paraffin embedding and were sectioned into 5 or 12 ㎛ ribbons for H&E staining and in situ hybridization, respectively. Results revealed teeth appearing in two maxillary rows: the labial side, with prefunctional and functional teeth, and the lingual side, with replaced tooth germs behind functional teeth. Enameloid was observed between the inner dental epithelium and dental mesenchyme at the cap or early bell stages, whereas enamel and dentin formed during the late bell or mineralization stages from the replaced tooth germ. Bmp4 expression was evident in the inner dental epithelium (ameloblasts), dental papilla (odontoblasts), stellate reticulum, and Hertwig's epithelial root sheath. Overall, these findings highlight the conservation of Bmp4 expression in X. laevis tooth development.

• Imaging Science in Dentistry
• /
• v.30 no.3
• /
• pp.169-181
• /
• 2000

Purpose: To investigate the expression of bone morphogenetic protein (BMP)-2/4 during eary tooth development after irradiation and calcium-deficient diet. Materials and Methods: The pregnant three-week-old Sprague-Dawley rats were used for the study. The control group was non-irradiation/normal diet group (Group 1), and the experimental groups were irradiation/normal diet group (Group 2) and irradiation/calcium-deficient diet group (Group 3). The abdomen of the rats at the 9th day of pregnancy were irradiated with single dose of 350 cGy. The rat pups were sacrificed at embryonic 18 days, 3 days and 14 days after delivery and the maxillae tooth germs were taken. The tissue sections of specimen were stained immunohisto-chemically with anti-BMP-2/4 antibody. Results: At embryo-18 days, immunoreacivity for BMP-2/4 of the Group 1 was modetate in stratum intermedium of dental organ and weak in dental papilla and dental follicle, but that of Group 2 was weak in cell layer of dental organ, and no immunoreacivity was shown in dental papilla and dental follice of Group 2 and in all tissue components of the Group 3. At postnatal-3 days, immunoreacivity for BMP-2/4 of the Group 1 was strong in cell layer of dental organ, odontoblasts and developing alveolar bone, but that of Group of 2 and Group 3 was weak in odontoblasts and developing alveolar bone. At postnatal-14 days, immunoreacivity for BMP-2/4 of the Group 1 was strong in newly formed cementum, alveolar bone and odontoblasts, but that of Group 2 was weaker than that of Group 1. In the Group 3, tooth forming cell layer showed weak immunoreactivity, but other cell layers showed no immunoreactivity. Couclusion : The expression of bone morphogenetic protein (BMP)-2/4 during early tooth development was disturbed after irradiation and calcium-deficient diet.

• BMB Reports
• /
• v.45 no.9
• /
• pp.509-514
• /
• 2012

We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with $TGF{\beta}1$ during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rh$TGF{\beta}1$ synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of $TGF{\beta}1$ inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of $TGF{\beta}1$ potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of $TGF{\beta}1$ decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that $TGF{\beta}1$ inhibits C3H10T1/2 proliferation in BMP9-induced osteogenesis and restricts the cells in $G_0/G_1$ phase. Our findings strongly suggest that $TGF{\beta}1$ may exert a biphasic effect on BMP9-induced osteogenic differentiation of mesenchymal stem cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.36 no.3
• /
• pp.161-171
• /
• 2010

Introduction: This study was to assess the effectiveness of new bone formation and regeneration by using a rhBMP-2 and $\beta-TCP$ as a carrier in rabbits’mandible. Materials and Methods: The mandibles of 36 rabbits were exposed and cortical bone was penetrated for this study. The experimental subjects were divided into 3 groups each 12 rabbits ; control group, experimental group 1, and experimental group 2. Control group had the defect itself without any treatment, in the experimental group 1, $\beta-TCP$P only was grafted, and in the experimental group 2, rhBMP-2 soaked in $\beta-TCP$ was grafted. The rabbits were sacrificed after 1, 2, 3, 4, 6, and 8weeks, and new bone formation area was examined and measured for bone quantitative and qualitative analysis with light, fluorescent and polarized microscopy. Results: In the experimental group 1, new bone formation from the adjacent host bone was made by osteoconduction, and in the experimental group 2, direct new bone formation by osteoinduction of rhBMP-2 as well as new bone formation by osteoconduction of $\beta-TCP$ were observed. Conclusion: rhBMP-2 of experimental group 2 is very effective in the bone formation in early 2weeks and bone remodelling from 3weeks.

• Korean Journal of Materials Research
• /
• v.24 no.12
• /
• pp.704-709
• /
• 2014

In this study, we fabricated a novel micro porous hybrid scaffold of biphasic calcium phosphate (BCP) and a polylectrolyte complex (PEC) of chitosan (CS) and hyaluronic acid (HA). The fabrication process included loading of CS-HA PEC in a bare BCP scaffold followed by lypophilization. SEM observation and porosimetry revealed that the scaffold was full of micro and macro pores with total porosity of more than 60 % and pore size in the range of $20{\sim}200{\mu}m$. The composite scaffold was mechanically stronger than the bare BCP scaffold and was significantly stronger than the CS-HA PEC polymer scaffold. Bone morphogenetic growth factor (BMP-2) was immobilized in CS-HA PEC in order to integrate the osteoinductive potentiality required for osteogenesis. The BCP frame, prepared by sponge replica, worked as a physical barrier that prolonged the BMP-2 release significantly. The preliminary biocompatibility data show improved biological performance of the BMP-2 immobilized hybrid scaffold in the presence of rabbit bone marrow stem cells (rBMSC).

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.28 no.4
• /
• pp.280-285
• /
• 2002

As the result of the study concerning "bone inducibility of chitosan", 1. "BMP-2" was observed mainly through the test when the "osteoblast" is exposed to the "chitosan". The expression of BMP-2 was 542.63 times compared to control after 2 hours exposure and it was maintained 16.60 times till 24 hours. 2. The expression of BMP-4 was decreased compared to control during exposure. 3. The expression of BMP-7 revealed two peaks during exposure. 4. The expression of osteocalcin was increased in early phase, and then decreased. Although it is not clear whether the "chitosan" is clinically effective material as a "bone induction material", we could say that it has a function for bone induction. Further detailed study will be required.

• Journal of Veterinary Clinics
• /
• v.40 no.2
• /
• pp.85-92
• /
• 2023

Fractures in the horse industry are challenging and a common cause of death in racehorses. To accelerate fracture healing, tissue engineering (TE) provides promising ways to regenerate bone tissues. This study aimed to evaluate the osteogenic effects of biphasic calcium phosphate collagen (BCPC) graft, bone morphogenetic protein 2 (BMP2), mesenchymal stem cell (MSC), and platelet-rich plasma (PRP) treatments in horses. Four thoroughbred horses were included in the study, and, in each horse, three cortical defects with a diameter of 5 mm and depth of 10 mm were formed in the third metacarpal bones (MC) and metatarsal bones (MT). The defects were randomly assigned to one of six treatment groups (saline, BCPC, BMP2, MSC, PRP, and control). Injections of saline, BMP2, PRP, or MSCs were made at 1, 3, and 5 weeks after defect surgery. Bone regeneration effects were assessed by radiography, quantitative computed tomography (QCT), micro-computed tomography (μCT), histopathological, and histomorphometric evaluation. The new bone ratio (%) in the histomorphometric evaluation was higher in the BMP2 group than in the control and saline groups. Radiographic and QCT values were significantly higher in the BCPC groups than in the other groups. QCT values of the BMP2 group were significantly higher than in the control and saline groups. The present study demonstrated that BCPC grafts were biologically safe and showed osteoconductivity in horses and the repeated injections of BMP2 without a carrier can be simple and promising TE factors for treating horses with bone fractures.