ABSTRACT
ObjectiveTo compare the effects of Taxillus chinensis from different hosts with different meridian affinity on bone microstructure and bone metabolism in ovariectomized osteoporotic rats， and investigate its mechanism of action. MethodEighty-eight specific-pathogen-free （SPF）-grade female Sprague-Dawley （SD） rats were selected and randomly divided into 11 groups： sham-operated group， model group， low-， medium- and high-dose groups of T. chinensis from Morus alba （2.5， 5， and 10 g·kg-1）， low-， medium- and high-dose groups of T. chinensis from Cinnamomum cassia （2.5， 5， and 10 g·kg-1）， and low-， medium- and high-dose groups of T. chinensis from C. burmannii （2.5， 5， and 10 g·kg-1）. After 12 weeks of drug intervention， the rats were examined for proximal femur bone density and bone microstructure using dual-energy X-ray absorptiometry （DXA） and micro-computed tomography （Micro-CT）. Histopathological changes in rat femur were observed by the hematoxylin-eosin staining （HE）. Contents of serum estradiol （E2）， bone Gla protein （BGP）， bone alkaline phosphatase （BALP）， tartrate-resistant acid phosphatase 5b （TRACP-5b） and pre-collagen type Ⅰ amino-terminal protopeptide （PINP） were measured by the enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to detect the messenger ribonucleic acid （mRNA） expressions of bone morphogenetic protein-2 （BMP-2）， Smad1， Smad9 and recombinant runt-related transcription factor 2 （Runx2） in rat humerus. Western blot was used to detect the protein expressions of BMP-2， p-Smad1/5/9 and Runx2 in rat humerus. ResultCompared with that in the sham-operated group， the femur microstructure of rats in the model group was significantly disrupted， with significant decreases in bone mineral density （BMD） value， bone volume fraction （BV/TV）， trabecular number （Tb.N）， and trabecular thickness （Tb.Th） （P<0.01）， and significant increases in trabecular separation （Tb.Sp） and structure model index （SMI） （P<0.01）. The serum levels of BGP， BALP， TRACP-5b and PINP were significantly increased （P<0.05， P<0.01）， and E2 levels were significantly decreased （P<0.01）. The mRNA expressions of BMP-2， Smad1， Smad9， and Runx2 were significantly decreased in rat humerus （P<0.01）， and the protein expressions of BMP-2， p-Smad1/5/9， and Runx2 were significantly reduced （P<0.01）. Compared with the model group， the administration groups of T. chinensis from different hosts all elevated the BMD， BV/TV， Tb.N， Tb.Th， Tb.Sp， and SMI levels in the femur， improved bone microstructure， increased serum E2 levels （P<0.05， P<0.01）， lowered the levels of serum BGP， BALP， TRACP-5b， and PINP， upregulated the mRNA expression of BMP-2， Smad1， and Runx2 and upregulated the mRNA expression levels of Smad9 （P<0.05， P<0.01）， and upregulated the protein expressions levels of BMP-2， p-Smad1/5/9， and Runx2 （P<0.01）. The best effect was observed in the group of T. chinensis from C. cassia. ConclusionT. chinensis from different hosts improved osteoporosis in ovariectomized rats， with the group of T. chinensis from C. cassia being the most potent among the administered groups， and its treatment of osteoporosis may regulate the balance of bone conversion by regulating BMP/Smad signaling pathway.
ABSTRACT
Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.
Subject(s)
Humans , Body Patterning , Bone Morphogenetic Protein Receptors/physiology , Bone Morphogenetic Proteins/physiology , Cell Differentiation , Cochlea/embryology , Ear, Inner/embryology , Hedgehog Proteins/physiology , Signal Transduction/physiology , Smad Proteins/physiology , Vestibule, Labyrinth/embryology , Wnt Signaling PathwayABSTRACT
Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.
ABSTRACT
[Objective]To discuss the initiating and developing mechanism of OPLL,and the influence of different operations on happening and developing of OPLL.[Method]We subgroup healthy adult S-D rats into groups,did operation on C 3~6 level.The first group:laminectomy;the second group:laminectomy and muscle cutting;the third group:muscle cutting only;the fourth group:exposure only;contrasting group:no treatment.We got the tissue of posterior longitudinal,ligament at 1,2,4,and 8 weeks post-operation and quantify BMP-2 and BMP-7 by PCR method.[Result]BMP-2,BMP-7 increased significantly in the 1st,2nd and 3rd group compared with the contrastinggroup;BMP-2,BMP-7 of only exposure group had no significant difference compared with the contrasting group.[Conclusion]BMP-2 and BMP-7 play important roles in the early stage of OPLL,they could be the on-setting factors of OPLL.BMP-7 may play an important roles in the later ossification period.
ABSTRACT
[Objective]To evaluate the effectiveness of recombinant human bone morphogenetic protein-2 in the repair of rabbit rotator cuff injury.[Method]Forty-eight male New Zealand rabbits,aged 8 months,received an rotator cuff acute injury and reconstruction of the insertion of supraspinatus tendon on greater tuberosity of humerus.The rabbits were randomly divided into 3 groups postoperatively:(1) rhBMP-2 group:fibrin sealant(FS) containing rhBMP-2 was applied to the interface between the bone-tendon interface; (2)FS control group:only FS was applied;(3)blank control group:untreated after the surgery.Harvested 36 specimens underwent biomechanical analysis at the 2nd,4th,8th postoperative weeks respectively.Harvested 12 specimens underwent histological analysis at the 8th postoperative week.[Result]Histological examination showed that Sharpey's fibers were found in the interface with the formation of four-layer indirect insertion in the rhBMP-2 group at the 8th postoperative week.In the FS control group and blank group,the tendon-bone interface was filled with granulation tissue and part of Sharpey's fibers and the newly generated bone tissue.Biomechanical analysis displayed that the tensile strength and stiffness of bone-tendon interface increased time-dependently in all groups,and it in the rhBMP-2 group was significantly higher than those in the other two groups at any time-points (both P
ABSTRACT
[Objective]To repair segmental bone defect with the composite of deproteinised cancellous bone,bone morphogenetic protein(BMP) and fibrin.[Method] Bone defects were created in 36 New Zealand rabbits on the bilateral radii and treated with three kinds of implantations:A,composite of deproteinised cancellous bone,BMP and fibrin;B,of deproteinised cancellous bone;C,blank control.The defects were observed by entgenography,optical microscopy,and electron-microscopy at 2,4,8,12,16 weeks.[Result] The defects treated with A implantation regenerated much more new bone and bridged earlier than the defects treated with B implantation and got completely repaired 16 weeks after operation.The defects with B and C implantation couldn't get osseous tissue healing.[Conclusion]The composite of deproteinised cancellous bone,bone morphogenetic protein(BMP) and fibrin can be effectively used to repair segmental bone defect.
ABSTRACT
@#ObjectiveTo observe the effect of rabbit skeletal muscle stem cells (RSMSCs) modified by adenovirus mediated bone morphogenetic protein-2 (BMP-2) gene ex vivo in combination with demineralized bone matrix (DBM) on repair of longer bone defect in rabbit.MethodsModel of radial bone defects (20 mm) of rabbits was established. 50 rabbits were divided into 5 groups, group A (AdrhBMP-2 trusduced RSMSCs/DBM group), group B (adGFP trusduced RSMSCs/DBM group), group C (not trusduced RSMSCs/DBM group), group D (DBM group), and group E (untreated group). Roentgenographic, histologic, biomechanical, bone density of all animals were examined at the end of 4th and 6th week after surgery.ResultsAt 4th week, radial bone defects healed in group A. The healing rates from group A to group E were 100%, 50%, 33%, 0%, and 0% respectively at 6th week.ConclusionRSMSCs modified by AdrhBMP-2 ex vivo in combination with DBM can repair radial longer segemental defect in rabbit. It's possible to be used in the clinical treatment of longer segemental bone defect.
ABSTRACT
PURPOSE: Bone morphogenetic protein (BMP) is a pleiotropic growth factor, which has been suggested to play a critical role during the development and homeostasis of the kidney. We evaluated the response of the human renal cell carcinoma (RCC) cell lines to BMPs. MATERIALS AND METHODS: We evaluated the growth rate of the human RCC cell lines, 112, 117 and 181, according to the concentrations of BMP-4, -6 and -7, and detected the levels of the BMP receptors (BMPRs) expressed in the cell lines. To demonstrate that the defect in BMP-6 signaling is at the receptor level, BMP-6 resistant cell lines were transfected, with adenovirus containing the constitutively active form of the BMP receptor types II (BMPR-II). After transfection, the cells were transfected with pSBE4, the construct of the BMP-6-responsive luciferase reporter gene, and a luciferase assay performed. RESULTS: The BMP-6 inhibited the proliferation of the 112, but not those of the 117 and 181 cells, in a dose-dependent manner. From Northern blot and immunoblot analyses, it was demonstrated that the 117 and 181 cells had undetectable levels of BMPR-II expression. The levels of luciferase activity, following adenovirus infections, was elevated in both the 117 and 181 cells, suggesting that the down-stream signaling molecules of the BMP-6 was intact in these cell lines. CONCLUSIONS: Taken together, these results demonstrate that the human RCC cell lines 117 and 181 are resistant to the growth inhibitory effects of the BMP-6 due to their decreased levels of BMPR-II expression.
Subject(s)
Humans , Adenoviridae , Adenoviridae Infections , Blotting, Northern , Bone Morphogenetic Protein 6 , Bone Morphogenetic Protein Receptors , Bone Morphogenetic Proteins , Carcinoma, Renal Cell , Cell Line , Genes, Reporter , Homeostasis , Kidney , Luciferases , TransfectionABSTRACT
The purpose of this study is to evaluate the influences of the bone morphogenetic protein (BMP) on the healing of periodontal ligament and alveolar bone after replantation of tooth, and to examine the possibility of its clinical application. 45 Sprague Dawley rats weighted about 100 gram were divided into 3 experimental groups by different dose of BMP. All the upper right and left 1st molar were extracted after 5 days feeding of 0.4% beta-aminopropionitrile, and right molar were used as experimental group and left molar were used as control group. The root surface of experimental molar were treated with 25, 50 and 100ng/ml of human recombinant Bone morphogenetic protein-4 (rh-BMP-4) with micropipet, and 1M Sodium hypochloride were used on control root surface. All the experimental animals were sacrificed as 1, 2, 4, 7 and 14 days after autoreplantation of upper 1st molar into their own position. The maxilla were disected included both side of 1st molar. The collected tissue were processed from demineralization to paraffin embeding as usual procedure, and the specimens were prepared with Hematoxylin-Eosin stain for the light microscopic evaluation. The results of this study were as follows : 1. There was no significant differences between control and experimental site on 1 and 2 days after replantation of tooth. In the case of 4th days, the evidence of tissue regeneration were observed on experimental site to compare the controls. New osteoid were revealed on high concentration of BMP at 7 days after replantation, and it became more obvious at 14 days. 2. The effect of the rh-BMP-4 coated on root surface was revealed slight influences for the prolifertion of cells of periodontium and tissue regeneration as dose-dependent pattern. 3. Bony ankylosis was observed between alveolar bone and root surface due to the remarkable amount of osteoid formation on the 14 days after replantation of root. In the conclusion, it was suggested that topical application of the rhBMP-4 on the root surface has influence on the periodontal ligament and alveolar bone. The application method of BMP on the root should be designed with calculation of proper concentration.
Subject(s)
Animals , Humans , Rats , Aminopropionitrile , Ankylosis , Bone Morphogenetic Proteins , Maxilla , Molar , Paraffin , Periodontal Ligament , Periodontium , Rats, Sprague-Dawley , Regeneration , Replantation , Sodium , Tooth Replantation , ToothABSTRACT
Objective To evaluate a new type of bone graft material made by combining bFGF,BMP with AACB in the clinic repair of ANFH(avascular necrosis of the femoral head)in animal experiments.Methods The combined material of bFGF/BMP/AACB was made and then this composite was transplanted to the models of canine femoral head defects and necrosis established by liquid nitrogen freezing,The specimens were harvested respectively at the end of three,six and 12 weeks after operation.A series of examinations were carried out to evaluate the repair results,including gross observation,radiography,histology,image pattern analy sis,blood vessel immuhistochemical staining,EDAX(energy dispersion analysis X-ray),and mechanical measurement.Results All the animals had no toxic or inflammatory reactions.Little new bone formed in group A(control group)by the end of 12 weeks.Group B(AACB group)was better than group A,and group C(BMP/AACB group)better than group B in osteogenesis.All the results showed that group D(bFGF/BMP/AACB group)was much superior to groups A,B and C in angiogenesis and osteogenesis at all intervals,and even better than group E(bone autograft group)by the end of three weeks and six weeks.By the end of 12 weeks,bone repairing and remodeling effects in group D were as good as in group E.Conclusions Since the bFGF/BMP/AACB compsite has great potential for enhacing revascularization and osteogenesis in repairing the defect and necrosis model of canine femoral head,it can be used as a substitute bone graft material for clinical patients with ANFH.
ABSTRACT
Objective:To study the feasibility of rapid tooth movement by periodontal ligament distraction osteogenesis. Method: Periodontal ligament distraction osteogenesis technology was applied on the experimental side; traditional orthodontic tooth movement technology on the control side in 8 dogs. The treatment was countinued for 14 days. Tooth movement and alveolar bone remodeling were studied by in vivo measuring,roentgenogram, histology and immunohistochemistry 2,3,6 and 10 weeks after treatment respectively. Results:2 weeks after application of treatment tooth movement(mm) with periodontal ligament distraction osteogenesis and that with traditional orthodontic method was 3.49?0.57 and 1.06?0.32 (P0.05) respectively. Active osteogenesis was obsered on the tension loaded side, BMP expression on the experimental tension-loaded side was stronger than that in the control side (P