Cited 21 times in
Can TGF-beta1 and rhBMP-2 act in synergy to transform bone marrow stem cells to discogenic-type cells?
DC Field | Value | Language |
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dc.contributor.author | 구성욱 | - |
dc.date.accessioned | 2015-05-19T17:31:59Z | - |
dc.date.available | 2015-05-19T17:31:59Z | - |
dc.date.issued | 2008 | - |
dc.identifier.issn | 0001-6268 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/108324 | - |
dc.description.abstract | INTRODUCTION: The recombinant human bone morphogenic protein-2 (rhBMP-2) is known to increase the proteoglycan production and chondrogenic gene expression in the disc cells. The transforming growth factor-beta 1 (TGF-beta(1)) can transform the bone marrow stem cells (BMDCs) into the disc-like cells. MATERIALS AND METHODS: We carried out an experiment to determine if TGF-beta(1) and rhBMP-2 can act in synergy on BMDCs by increasing the production of sulfated-glycosaminoglycan (sGAG) and affecting the mRNA expression of aggrecan, type I collagen, and type II collagen. The BMDCs were isolated from the iliac crest and femur of a New Zealand white rabbit (1 year). The BMDCs were culured in monolayer and treated for 6 days with TGF-beta(1) 10 ng/ml (group 1), rhBMP-2 200 ng/ml (group 2), and both TGF-beta(1) 10 ng/ml and rhBMP-2 200 ng/ml (group 3: the combined group) in Dulbecco's modified Eagle medium/F-12 with 1% fetal bovine serum. After 6 days, the sGAG content in the media was quantified using 1,9-dimethylmethylene blue staining and the mRNA expression of aggrecan, type I collagen, type II collagen, Sox-9, BMP-2, and BMP-7 were measured with the real-time PCR. The same BMDCs were also cultured in the chamber slide at 3 x 10(4) cells/chamber. After 6 days treatment, the treated cells were immunofluorescence stained with aggrecan, type I collagen, type II collagen, anti-BMP-2, anti-BMP-7 antibodies. After that, we compared the number of positive immunofluorescence stained cells with fluorescence microscope. The sGAG production and mRNA expression for each group were normalized against the same parameters for a non-treatment group. RESULTS AND DISCUSSION: The sGAG production was increased 1.15*, 1.34*, and 1.45* times in the TGF-beta(1) 10 ng/ml group, the rhBMP-2 200 ng/ml group, and the combined group respectively. The mRNA expression of aggrecan was increased 1.28, 3.42*, and 5.34* times, the mRNA expression of type I collagen was increased 0.86, 1.09, 1.17 times, the mRNA expression of type II collagen was increased 3.58*, 3.77*, and 10.78* times, the mRNA expression of Sox-9 was increased 1.29, 2.45, 2.75* times, the mRNA expression of BMP-2 was increased 1.14, 2.07, 4.43* times, and the mRNA expression of BMP-7 was increased 1.16, 1.49, 1.97* times, respectively for each group (* indicates p < 0.05). On the immunofluorescence staining of antibodies, the average positively immunofluorescence stained cells number for aggrecan were 4.2, 15.8*, 10*, and 22* according to the non-treatment group, TGF-beta(1) 10 ng/ml group, rhBMP-2 200 ng/ml group, and the combined group respectively. The average positively immunofluorescence stained cells number for type I collagen were 7, 14.2*, 9.2*, 17.4* and the average positively immunofluorescence stained cells number for type II collagen were 8.5, 28.25*, 20.25*, 42.25* and the average positively immunofluorescence stained cells number for anti-BMP-2 were 5, 16.75*, 8.75*, 27.25* and the average positively immunofluorescence stained cells number for anti-BMP-7 were 3.25, 7.5*, 8.75*, 15.25* (* indicates p < 0.05). CONCLUSIONS: Both TGF-beta(1) and rhBMP-2 alone, can increase proteoglycan production in the BMDCs. However, if they were used in combination, there is a synergistic effect. Similarly, the mRNA expressions of both aggrecan, type II collagen, Sox-9, BMP-2, and BMP-7 except for type I collagen were increased significantly when TGF-beta(1) and rhBMP-2 were combined. The positive immunofluorescence stained cell numbers for aggrecan, type I, II collagen, BMP-2 and BMP-7 were also increased after each TGF-beta(1) and rhBMP-2 treatment, and also more increased significantly in the aggrecan, type I, II collagen, BMP-2, and 7 when they were used jointly. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1073~1079 | - |
dc.relation.isPartOf | ACTA NEUROCHIRURGICA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Aggrecans/genetics | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Bone Marrow Cells/cytology | - |
dc.subject.MESH | Bone Marrow Cells/drug effects* | - |
dc.subject.MESH | Bone Marrow Cells/metabolism | - |
dc.subject.MESH | Bone Marrow Transplantation/methods | - |
dc.subject.MESH | Bone Morphogenetic Protein 2/pharmacology* | - |
dc.subject.MESH | Bone Morphogenetic Protein 2/therapeutic use | - |
dc.subject.MESH | Bone Morphogenetic Protein 7/genetics | - |
dc.subject.MESH | Cell Culture Techniques/methods | - |
dc.subject.MESH | Cell Differentiation/drug effects* | - |
dc.subject.MESH | Cell Differentiation/physiology | - |
dc.subject.MESH | Chondrogenesis/drug effects* | - |
dc.subject.MESH | Chondrogenesis/physiology | - |
dc.subject.MESH | Collagen Type I/genetics | - |
dc.subject.MESH | Collagen Type II/genetics | - |
dc.subject.MESH | Drug Synergism | - |
dc.subject.MESH | Glycosaminoglycans/biosynthesis | - |
dc.subject.MESH | Intervertebral Disc/cytology | - |
dc.subject.MESH | Intervertebral Disc/drug effects | - |
dc.subject.MESH | Intervertebral Disc/metabolism | - |
dc.subject.MESH | Intervertebral Disc Displacement/metabolism | - |
dc.subject.MESH | Intervertebral Disc Displacement/pathology | - |
dc.subject.MESH | Intervertebral Disc Displacement/surgery | - |
dc.subject.MESH | RNA, Messenger/drug effects | - |
dc.subject.MESH | RNA, Messenger/metabolism | - |
dc.subject.MESH | Rabbits | - |
dc.subject.MESH | Recombinant Fusion Proteins/pharmacology | - |
dc.subject.MESH | Recombinant Fusion Proteins/therapeutic use | - |
dc.subject.MESH | Regeneration/drug effects | - |
dc.subject.MESH | Regeneration/physiology | - |
dc.subject.MESH | Stem Cells/cytology | - |
dc.subject.MESH | Stem Cells/drug effects* | - |
dc.subject.MESH | Stem Cells/metabolism | - |
dc.subject.MESH | Transforming Growth Factor beta1/pharmacology* | - |
dc.subject.MESH | Transforming Growth Factor beta1/therapeutic use | - |
dc.title | Can TGF-beta1 and rhBMP-2 act in synergy to transform bone marrow stem cells to discogenic-type cells? | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Neurosurgery (신경외과학) | - |
dc.contributor.googleauthor | Kuh SU | - |
dc.contributor.googleauthor | Zhu Y | - |
dc.contributor.googleauthor | Li J | - |
dc.contributor.googleauthor | Tsai KJ | - |
dc.contributor.googleauthor | Fei Q | - |
dc.contributor.googleauthor | Hutton WC | - |
dc.contributor.googleauthor | Yoon ST. | - |
dc.identifier.doi | 10.1007/s00701-008-0029-z | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00196 | - |
dc.relation.journalcode | J00018 | - |
dc.identifier.eissn | 0942-0940 | - |
dc.identifier.pmid | 18781274 | - |
dc.identifier.url | http://link.springer.com/article/10.1007/s00701-008-0029-z | - |
dc.subject.keyword | Proteoglycan | - |
dc.subject.keyword | Bone marrow derived cells | - |
dc.subject.keyword | TGF-β1 | - |
dc.subject.keyword | rhBMP-2 | - |
dc.contributor.alternativeName | Kuh, Sung Uk | - |
dc.contributor.affiliatedAuthor | Kuh, Sung Uk | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 150 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1073 | - |
dc.citation.endPage | 1079 | - |
dc.identifier.bibliographicCitation | ACTA NEUROCHIRURGICA, Vol.150(10) : 1073-1079, 2008 | - |
dc.identifier.rimsid | 35488 | - |
dc.type.rims | ART | - |
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