• The Journal of the Korean dental association
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• v.46 no.8
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• pp.494-504
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• 2008

Osseointegration is a result of bone formation and bone regeneration process, which take place at the interface between bone and implant and biologic determinants such as cytokine, growth factors, bone matrix proteins play an important role in osseointegration. The purpose of this study is to compare the expressoin of TGF-$\beta$, IGF-I, BMP2, BMP4 during osseointegration. We designed an experimental group which was inserted with a RBM surface titanium implants and machined surface, and compared with a control group which had a simple bone cavity and normal bone. Titanium implants were placed into tibia of 8 rabbits. We compared the expression of TGF-$\beta$, IGF-I, BMP2, BMP4 using RT_PCR (reverse transcriptase chain reaction)analysis in day 3,7,14 and 28 of implant insertion. According to the results, growth factors of experimental groups were more expressed than control groups. Among experimental groups, expression of TGF-$\beta$, IGF-I, BMP4 of BMP group had tedency to increase more at 14th, 28th days than Machined surface group. Therefore, our results suggest that TGF-$\beta$, IGF-I, BMP4 are expressed within the bone around the implant and more increased around rough surface implants while osseointegration occurs after dental implant insertion.

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

• Korean Journal of Poultry Science
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• v.44 no.3
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• pp.211-223
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• 2017

Transforming growth factor beta ($TGF-{\beta}$) signaling pathways are involved in the regulation of proliferation, differentiation, immunity, survival, and apoptosis of many cells. The aim of this study was to investigate the differential expression of $TGF-{\beta}$-related genes, and their interactions and regulators in the spleen of two genetically disparate chicken lines (Marek's disease resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE) by Eimeria maxima and Clostridium perfringens infection. By using high-throughput RNA-sequencing, we investigated 76 $TGF-{\beta}$-related genes that were significantly and differentially expressed in the spleens of the chickens. Approximately 20 $TGF-{\beta}$ pathway genes were further verified by qRT-PCR, and the results were consistent with our RNA sequencing data. All 76 identified genes were analyzed through Gene Ontology and mapped onto the KEGG chicken $TGF-{\beta}$ pathway. Our results demonstrated that several key genes, including $TGF-{\beta}$1-3, bone morphogenetic proteins (BMP)1-7, inhibitor of differentiation (ID) proteins ID1-3, SMAD1-9, and Jun, showed a markedly differential expression between the two chicken lines, relative to their respective controls. We then further predicted 24 known miRNAs that targeted BMP7 mRNA from 139 known miRNAs in the two chicken lines. Among these, six miRNAs were measured by qRT-PCR. In conclusion, this study is the first to analyze most of the genes, interactions, and regulators of the $TGF-{\beta}$ pathway in the innate immune responses of NE afflicted chickens.

• Journal of Chest Surgery
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• v.36 no.2
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• pp.86-90
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• 2003

Bulla is an air-filled space within the lung parenchyma resulting from deterioration of the alveolar tissue. Molecular mechanism of the formation of the bulla is not well described. Fibroblast growth factor(FGF)-7, bone morphogenetic protein(BMP) receptor, and transforming growth factor(TGF)-$\beta$ receptor are known to have a stimulatory or inhibitory role in the lung formation. We investigated to see if these growth factor or cytokine receptors are involved in the bulla formation by immunohistochemical staining of bullous lung tissues from patients with primary spontaneous pneumothorax. Material and Method: Bullous lung tissues were obtained from 31 patients with primary spontaneous pneumothorax, including 30 males and 1 female from 15 to 39 years old. The bullous tissues were obtained by video-thoracoscopic surgery and/or mini-thoracotomy and fixed in formalin. Blocks of the specimens were embedded with paraffin and cut into 5-6 ${\mu}{\textrm}{m}$ thick slices. The sections were deparaffinized and hydrated and then incubated with primary antibodies against FGF-7, BMP-RII, or TGF-RII. Result: Of the 31 patients, 24 were TGF-RII positive including 18 strong and 6 weak positives. Observation with high magnification showed that strong immunostaining was detected in the boundary region between bullous and normal lung tissues. In contrast, all of the sections were negative with FGF-7 or BMP-RII antibodies. Conclusion: These results suggest that overexpression of TGF- P RII may be involved in the formation of bulla, although further molecular studies are needed to find out more detailed molecular mechanisms.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.4
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• pp.477-484
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• 2019

Objective: We aimed to observe hair follicle (HF) development in the dorsal skin and elucidate the expression patterns of genes and proteins related to skin and HF development in Rex rabbits from birth to 8 weeks of age. Methods: Whole-skin samples were obtained from the backs of Rex rabbits at 0, 2, 4, 6, and 8 weeks of age, the morphological development of primary and secondary HFs was observed, and the gene transcript levels of insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), bone morphogenetic protein 2 (BMP2), transforming growth factor ${\beta}-1$, 2, and 3 ($TGF{\beta}-1$, $TGF{\beta}-2$, and $TGF{\beta}-3$) were examined using quantitative real-time polymerase chain reaction (PCR). Additionally, Wnt family member 10b (Wnt10b) and ${\beta}$-Catenin gene and protein expression were examined by quantitative real-time PCR and western blot, respectively. Results: The results showed significant changes in the differentiation of primary and secondary HFs in Rex rabbits during their first 8 weeks of life. The IGF-I, EGF, $TGF{\beta}-2$, and $TGF{\beta}-3$ transcript levels in the rabbits were significantly lower at 2 weeks of age than at birth and gradually increased thereafter, while the BMP2 and $TGF{\beta}-1$ transcript levels at 2 weeks of age were significantly higher than those at birth and gradually decreased thereafter. ${\beta}$-Catenin gene expression was also significantly affected by age, while the Wnt10b transcript level was not. However, the Wnt10b and ${\beta}$-catenin protein expression levels were the lowest at 2 and 4 weeks of age. Conclusion: Our data showed that a series of changes in HFs in dorsal skin occurred during the first 8 weeks. Many genes, such as IGF-I, EGF, BMP2, $TGF{\beta}-1$, $TGF{\beta}-2$, $TGF{\beta}-3$, and ${\beta}$-Catenin, participated in this process, and the related proteins Wnt10b and ${\beta}$-Catenin in skin were also affected by age.

• BMB Reports
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• v.38 no.1
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• pp.9-16
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• 2005

Transforming Growth Factor (TGF)-$\beta$ family, including TGF-$\beta$, bone morphorgenic protein (BMP), and activn, plays an important role in essential cellular functions such as proliferation, differentiation, apoptosis, tissue remodeling, angiognesis, immune responses, and cell adhesions. TGF-$\beta$ predominantly transmits the signals through serine/threonine receptor kinases and cytoplasmic proteins called Smads. Since the discovery of TGF-$\beta$ in the early 1980s, the dysregulation of TGF-$\beta$/Smad signaling has been implicated in the pathogenesis of human diseases. Among signal transducers in TGF-$\beta$/Smad signaling, inhibitory Smads (I-Smads), Smad6 and Smad7, act as major negative regulators forming autoinhibitory feedback loops and mediate the cross-talking with other signaling pathways. Expressions of I-Smads are mainly regulated on the transcriptional levels and post-translational protein degradations and their intracellular levels are tightly controlled to maintain the homeostatic balances. However, abnormal levels of I-Smads in the pathological conditions elicit the altered TGF-$\beta$ signaling in cells, eventually causing TGF-$\beta$-related human diseases. Thus, exploring the molecular mechanisms about the regulations of I-Smads may provide the therapeutic clues for human diseases induced by the abnormal TGF-$\beta$ signaling.

• Clinical and Experimental Reproductive Medicine
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• v.34 no.4
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• pp.239-252
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• 2007

Objectives: In the present study, we examined the differentiation potential of human adipose-(HAD) and human umbilical cord-derived mesenchymal like stem cells (HUC) into cardiomyocytes. Methods: Cells were initially exposed to 5-azacytidine for 24h cells and then were cultivated in the presence or absence of activin A, TGF-$\beta$1, or Wnt inhibitor with various combinations of BMP and FGF. Assessment of cardiomyogenic differentiation was made upon the expression of cardiomyocyte-specific genes using RT-PCR. Results: HAD that cultivated in control medium for 4 weeks after 5-azacytidine expose showed new expression of TnT gene and increased expression of Cmlc1 and kv4.3 genes. However, HAD cultivated in the presence of combinations of BMP-4/FGF-4 (B4/F4) and BMP-4/FGF-8 (B4/F8) showed new expression of $\beta$-MHC gene and more increased expression of Cmlc1, TnT, TnI, Kv4.3 genes. Significantly enhanced expression of Cmlc1, TnT, and Kv4.3 genes were also observed compared to that cultivated in the control medium. Treatment of HUC with either 5-azacytidine or combinations of BMP and FGF did not affect the expression profile of these genes. However, when activin A or TGF-$\beta$1 was present in addition to the BMP-2/FGF-8 (B2/F8) after 5-azacytidine exposure, HUC exhibited new expression of $\beta$-MHC gene and increased expression of $\alpha$-CA, TnT and Kv4.3 genes. When Wnt inhibitor was present in addition to BMP and FGF, HUC showed new expression of Cmlc1 gene and increased expression of $\alpha$-CA, TnT, TnI and Kv4.3 genes. Conclusions: Based on these observations, it is suggested that HAD and HUC could differentiate into cardiomyocytes which might be used as therapeutic cells for the heart diseases.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.2
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• pp.73-81
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• 2013

Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$/bone morphogenetic protein ($TGF-{\beta}/BMP$) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4. Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$). Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice. Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.4
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• pp.288-296
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• 2007

Distraction osteogenesis(DO) is a technique of lengthning bone including soft tissue by gradual separation of surgically divided bone surfaces. Distraction osteogenesis combination with a compression stimulation(DO-CO) was a new technique by authors to enhance new bone quality and to shorten the consolidation period. The purpose of this study was to compare DO with DO combined with compression force in efficiency by evaluating the expression of TGF-${\beta}1$, osteonectin and BMP-4 on bone regenerate in rabbit mandible. Fourty two rabbits were used for this experiment. On the control group, the distraction was carried out at the rate of 1 mm per day to obtain the amount of 8 mm distraction for 8 days. On the experimental group, the distraction was carried out at the rate of 1 mm per day for 10 days, 3 days-latency period, and then the compression was carried out as counter direction 1 mm per day for 2 days. After 0 day, 5 days, 13 days, 20 days, 27 days, 34 days and 41 days, three rabbits on each group were sacrificed and the distracted portion of mandible were cut and treated for RT-PCR observation. The level of expression of TGF-${\beta}1$ and osteonectin were shown more and longer expression in the experimental group than in the control group. The expression of BMP-4 was maintained with high level during the entire experimental period in both groups. These findings suggested that DO with compression stimulation could be a favorable technique for obtaining a good new bone quality.

• BMB Reports
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• v.46 no.2
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• pp.107-112
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• 2013

Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II $TGF{\beta}$ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional $TGF{\beta}$ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.