Potent Ectopic Bone-Inducing Activity of Bone Morphogenetic Protein-4/7 Heterodimer

Aono, Aki; Hazama, Masatoshi; Notoya, Kohei; Taketomi, Shigehisa; Yamasaki, Hitomi; Tsukuda, Ryoichi; Sasaki, Shigekazu; Fujisawa, Yukio

doi:10.1006/bbrc.1995.1712

Cited by 234 publications

(146 citation statements)

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“…This interpretation of the roles of BMPs in testis development by examination of BMP-mutant testes is further complicated by the prospect that the absence of one BMP gene results in both the loss of homodimers of the BMP under investigation and of the more potent heterodimers formed with other BMPs (Aono et al, 1995;Israel et al, 1996;Suzuki et al, 1997;Zhu et al, 2006); how this impacts on the regulation of gene expression in the testis needs further examination.…”

Section: Fig 11 Amentioning

confidence: 99%

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

Itman

Loveland

2007

Developmental Dynamics

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Bone morphogenetic proteins (BMPs), members of the transforming growth factor-␤ superfamily, extensively influence events that establish male fertility, affecting germ cells and somatic cells throughout fetal and postnatal life. BMP signals are relayed by SMAD proteins, transcription factors that translocate to the nucleus upon ligand stimulation. We show that BMP signaling in the testis may be regulated by selective expression of BMP-responsive and inhibitory SMADs, with expression differing between the first wave and adult spermatogenesis. Smad1, Smad5, Smad8, Smad4, Smad6, and Smad7 expression is ubiquitous during testis development but becomes cell-specific in the adult. Furthermore, regulated SMAD6 protein expression at the onset of spermatogenesis suggests differential responsiveness of spermatogonial subpopulations to ligands. In vitro, immature Sertoli cells and spermatogonia transduce BMP2 and BMP4 signals by means of SMAD1, SMAD5, and SMAD8. Based on these findings, we extrapolate these data to interpret BMP mutant testis phenotypes in terms of SMAD availability for signal transduction. Developmental Dynamics 237:97-111, 2008.

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Section: Fig 11 Amentioning

confidence: 99%

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

Itman

Loveland

2007

Developmental Dynamics

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“…The BMP-7 vector induced only weak alkaline phosphatase activity. 35,36 Recombinant BMP adenoviruses have been the most commonly used vectors in BMP gene therapy. Direct injection of recombinant BMP-2 adenovirus can induce bone formation in immunodefective and immunocompetent mice and athymic nude rats, but could not stimulate ectopic bone formation in Sprague-Dawley rats.…”

Section: Introductionmentioning

confidence: 99%

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

et al. 2003

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one morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague-Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 Â 10 5 PFU/well of BMP viral vector was 4890 Â 10 À12 U/well for ADCMVBMP-9, 302 Â 10 À12 U/well for ADCMVBMP-4, 220 Â 10 À12 U/well for ADCMVBMP-6, 45 Â 10 À12 U/well for ADCMVBMP-2, and 0.43 Â 10 À12 U/ well for ADCMVBMP-7. The average volume of new bone induced by 10 7 PFU of BMP vector in athymic nude rats was 0.3770.03 cm 3 for ADCMVBMP-2, 0.8970.07 cm 3 for ADCMVBMP-4, 1.0270.07 cm 3 for ADCMVBMP-6, 0.2470.05 cm 3 for ADCMVBMP-7, and 0.6370.07 cm 3 for ADCMVBMP-9. In immunocompetent Sprague-Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 10 8 PFU induced 0.1070.03 cm 3 of new bone, whereas ADCMVBMP-9 at a lower viral dose of 10 7 PFU induced more bone, with an average volume of 0.2970.01 cm 3 .

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“…As with all TGF-β family members, BMP-4 is synthesized as an inactive precursor and is proteolytically activated by cleavage following the multibasic amino acid motif -Arg-Ser-Lys-Arg-to yield a C-terminal mature protein dimer (Aono et al, 1995). This processing event has been proposed to regulate the secretion and/or diffusion of BMPs, thereby controlling the range over which these molecules can signal during embryonic development (Jones et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development

et al. 1998

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Potent Ectopic Bone-Inducing Activity of Bone Morphogenetic Protein-4/7 Heterodimer

Cited by 234 publications

References 0 publications

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

SMAD expression in the testis: An insight into BMP regulation of spermatogenesis

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development

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