The time course study of osteoinduction by bone morphogenetic protein-2 via adenoviral vector

Life Sciences ◽  
2001 ◽  
Vol 70 (3) ◽  
pp. 325-336 ◽  
Author(s):  
Yasunori Okubo ◽  
Kazuhisa Bessho ◽  
Kazuma Fujimura ◽  
Shinji Kaihara ◽  
Tadahiko Iizuka ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Adenoviral Vector ◽  
Time Course ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Time Course Study

scholarly journals Bone Morphogenetic Protein-2 Antagonizes Renal Interstitial Fibrosis by Promoting Catabolism of Type I Transforming Growth Factor-β Receptors

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 727-740 ◽  
Author(s):  
Yu-Lin Yang ◽  
Yi-Shiuan Liu ◽  
Lea-Yea Chuang ◽  
Jinn-Yuh Guh ◽  
Tao-Chen Lee ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Ureteral Obstruction ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Morphogenetic Protein ◽  
Tgf Β1

TGF-β is a therapeutic target for renal fibrosis. Scientists have long sought ways to antagonize TGF-β to ameliorate diabetic nephropathy. Bone morphogenetic protein (BMP-2) is a member of the TGF-β superfamily and is highly regulated in the kidney. Thus, the role of BMP-2 was investigated in NRK-49F cells (rat fibroblasts). We showed that TGF-β1 induces an increase in fibronectin. Treatment with exogenous BMP-2 or pCMV-BMP-2 significantly reversed the TGF-β1-induced increase in fibronectin concomitant with a significant decrease in type I TGF-β receptors (TGF-β RI). Moreover, BMP-2 significantly shortened the half-life of TGF-β RI. These results are related to proteosomal activation because MG132, a proteasome inhibitor, abolished BMP-2-mediated degradation of TGF-β RI. This was confirmed because BMP-2 time course dependently enhanced the ubiquitination level of TGF-β RI. In addition, Smads would seem to be involved in the interaction of BMP-2 and TGF-β. We demonstrated that BMP-2 significantly reversed the TGF-β1-induced increase in pSmad2/3 and reversed the TGF-β1-induced decrease in inhibitory Smad7. Most importantly, Smad7 small interfering RNA abolished the BMP-2-induced decrease in TGF-β RI. We evaluated the clinical efficacy of BMP-2 using unilateral ureteral obstruction rats. BMP-2 was administered ip for 7 d. In the unilateral ureteral obstruction kidneys, interstitial fibrosis was prominent. However, treatment with BMP-2 dramatically reduced Masson’s trichrome staining (collagen) in the interstitial and tubular areas of the kidneys concomitantly with a reduction in TGF-β RI. These results suggest that BMP-2 acts as a novel fibrosis antagonizing cytokine partly by down-regulating TGF-β RI and Smads. Bone morphogenetic protein-2 can antagonize TGF-β-inducing cellular fibrosis by intervening post-receptors signaling, thus disclosing an application of therapeutical potential against fibrosis disorders.

Bone morphogenetic protein 2 stimulates chondrogenesis of equine synovial membrane-derived progenitor cells

2016 ◽  
Vol 29 (05) ◽  
pp. 378-385 ◽  
Author(s):  
Yuwen Chen ◽  
Evelyn Caporali ◽  
Matthew Stewart
Keyword(s):  
Progenitor Cells ◽  
Bone Morphogenetic Protein ◽  
Synovial Membrane ◽  
Adenoviral Vector ◽  
Collagen Type ◽  
Bone Morphogenetic Protein 2 ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Potent Inducer ◽  
Morphogenetic Protein

SummaryObjectives: Bone morphogenetic protein 2 (BMP-2) is critical for skeletal and cartilage development, homeostasis and repair. This study was conducted to clone and characterize equine BMP-2, develop expression constructs for equine BMP-2, and to determine whether BMP-2 can stimulate chondrogenesis of equine synovial membrane-derived progenitor cells (SMPC).Methods: Equine BMP-2 cDNA was amplified from chondrocyte RNA, and then transferred into an expression plasmid and adenoviral vector. Effective expression of equine BMP-2 was confirmed using a BMP reporter cell line. SMPC were isolated from synovium, expanded through two passages and transferred to chondrogenic cultures, with recombinant human (rh) transforming growth factor beta 1 (TGF-[uni03B2]1) or rhBMP-2. Chondro-genesis was assessed by up-regulation of collagen types II and X, and aggrecan mRNA, secretion of collagen type II protein and sulfated glycosaminoglycans (sGAG), and by alkaline phosphatase induction. Chondrogenic stimulation of SMPC by the equine BMP-2 adenovirus was assessed by sGAG secretion and histology.Results: The mature equine BMP-2 peptide is identical to human and murine peptides. Recombinant human BMP-2 and TGF-[uni03B2]1 stimulated equivalent amounts of collagen type II protein in SMPC pellets, but sGAG secretion was doubled by BMP-2. Neither factor stimulated hypertrophic marker expression. The equine BMP-2 adenoviral vector induced chondrogenesis comparably to rhBMP-2 protein, with no indication of hypertrophy.Clinical significance: Bone morphogenetic protein 2 is a potent inducer of SMPC nonhypertrophic chondrogenesis, supporting the use of this combination for articular cartilage repair applications.

In Vitro and in Vivo Studies of a Bone Morphogenetic Protein-2 Expressing Adenoviral Vector

2001 ◽  
Vol 83 ◽  
pp. S1-99-S1-104 ◽  
Author(s):  
Yasunori Okubo ◽  
Kazuhisa Bessho ◽  
Kazuma Fujimura ◽  
Tadahiko Iizuka ◽  
Shin-ichi Miyatake
Keyword(s):  
Bone Morphogenetic Protein ◽  
Adenoviral Vector ◽  
Bone Morphogenetic Protein 2 ◽  
In Vivo Studies ◽  
Morphogenetic Protein

Osteoinduction by Bone Morphogenetic Protein-2 via Adenoviral Vector under Transient Immunosuppression

2000 ◽  
Vol 267 (1) ◽  
pp. 382-387 ◽  
Author(s):  
Yasunori Okubo ◽  
Kazuhisa Bessho ◽  
Kazuma Fujimura ◽  
Tadahiko Iizuka ◽  
Shin-Ichi Miyatake
Keyword(s):  
Bone Morphogenetic Protein ◽  
Adenoviral Vector ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein
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