Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2.

Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Research Abstract Details 

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Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Abstract Text:

S Mori,H Yoshikawa,J Hashimoto,T Ueda,H Funai,M Kato,K Takaoka,

Bone morphogenetic protein (BMP) is a potent inducer of ectopic bone formation, and TNP-470, a synthetic analog of fumagillin, is an antiangiogenic agent that strongly inhibits neovascular formation in vivo. We investigated the effects of TNP-470 on BMP-induced ectopic bone formation to clarify the role of angiogenesis in bone formation. Collagen pellets containing recombinant human BMP-2 (rhBMP-2) were implanted beneath the fasciae of dorsal muscles in mice. By daily subcutaneous administration of TNP-470, ectopic new bone formation was inhibited in a dose-dependent manner. Histological examination revealed that TNP-470 prevented proliferation of mesenchymal cells and chondrogenesis at the initial step of endochondral bone formation. Immunohistochemical staining with a specific antibody against bone morphogenetic protein type IA receptor showed that TNP-470 reduced the number of receptor-positive cells surrounding the BMP pellets. The inhibitory effect of TNP-470 on bone formation continued during the period of its administration, and discontinuation of treatment was followed by the resumption of the whole process of endochondral bone formation. This study showed that TNP-470 reversibly inhibits the biological activity of rhBMP-2 in the early stage of bone induction, suggesting that angiogenesis may play an essential role in the recruitment of BMP-receptor-positive cells that can respond to rhBMP-2 and differentiate into chondrocytes and/or osteoblasts.

Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Publishing Authors By Initials

S Mori,H Yoshikawa,J Hashimoto,T Ueda,H Funai,M Kato,K Takaoka,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bone

VOLUME: 22

Page Numbers: 99-105

Journal Abbreviation: Bone

ISSN: 8756-3282

DAY: 19

MONTH: Feb

YEAR: 1998

Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Information

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LANGUAGE: eng

NlmUniqueID: 8504048

Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Information

Substance Name: Protein-Serine-Threonine Kinases

Registry Number: EC 2.7.11.1

Grant and Affiliation Information for Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2.

AFFILIATION: Department of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.

Country: UNITED STATES

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MEDLINETA: Bone

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