Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development.

Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Research Abstract Details 

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Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Abstract Text:

Mina Okamoto,Junko Murai,Hideki Yoshikawa,Noriyuki Tsumaki,

In this study, overexpression of noggin, a BMP antagonist, in developing bone caused significantly decreased osteoclast number as well as bone formation rate, resulting in increased bone mass with immature bone quality. BMP signaling plays important roles in normal bone development and regulation of bone resorption. INTRODUCTION: Bone morphogenetic proteins (BMPs) act on various types of cells. Although involvement of BMP signals in osteoblast differentiation has been studied extensively, the effects of BMPs on osteoclasts have not been widely researched. Consequently, the net effects of BMPs on bone remain unclear. The purpose of this study was to delineate more fully the role of BMPs in skeletal biology. MATERIALS AND METHODS: We generated transgenic mice that express BMP4 or noggin in bone under the control of the 2.3-kb alpha1(I) collagen chain gene (Col1a1) promoter, and analyzed their bone phenotype. We also analyzed bone of transgenic mice expressing BMP4 specifically in cartilage. RESULTS: Mice overexpressing BMP4 in bone developed severe osteopenia with increased osteoclast number. Mice overexpressing noggin, a BMP antagonist, in bone showed increased bone volume associated with decreased bone formation rate and decreased osteoclast number. The noggin-transgenic tibias exhibited reduced periosteal bone formation and reduced resorption of immature bone in marrow spaces, associated with frequent fractures at the diaphysis. Co-culture of primary osteoblasts prepared from noggin-transgenic calvariae and wildtype spleen cells resulted in poor osteoclast formation, which was rescued by addition of recombinant BMP2, suggesting that noggin inhibits osteoclast formation by attenuating BMP activities in noggin-transgenic mice. The expression levels of Rankl were not decreased in primary osteoblasts from noggin transgenic mice. Immunoblot analysis showed increased phosphorylation of Smad1/5/8 in osteoclast precursor cells after 20-minute treatment with BMPs, suggesting that these cells are stimulated by BMPs. Mice overexpressing BMP4 in cartilage had enlarged bones containing thick trabeculae, possibly because of expansion of cartilage anlagen. CONCLUSIONS: Overexpression of noggin in bone revealed that BMP signals regulate bone development through stimulation of osteoblasts and osteoclasts.

Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Publishing Authors By Initials

M Okamoto,J Murai,H Yoshikawa,N Tsumaki,

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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Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of bone and mineral research : the officia

VOLUME: 21

Page Numbers: 1022-33

Journal Abbreviation: J. Bone Miner. Res.

ISSN: 0884-0431

DAY: 19

MONTH: Jul

YEAR: 2006

Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Information

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LANGUAGE: eng

NlmUniqueID: 8610640

Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: metabolism

Chemical & Substance for Abstract: Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. Information

Substance Name: noggin protein

Registry Number: 148294-77-3

Grant and Affiliation Information for Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development.

AFFILIATION: Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Country: United States

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MEDLINETA: J Bone Miner Res

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