AMBN and Osteogenesis Bone revised.pdf (424.56 kB)

Ameloblastin Modulates Osteoclastogenesis through the Integrin/ERK Pathway

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journal contribution
posted on 03.12.2013 by Xuanyu Lu, Yoshihiro Ito, Phimon Atsawasuwan, Smit Dangaria, Xiulin Yan, Tuojiang Wu, Carla A. Evans, Xianghong Luan
Proteins of the extracellular matrix often have multiple functions to facilitate complex tasks ranging from signaling to structural support. Here we have focused on the function of one of the matrix proteins expressed in bones and teeth, the matrix adhesion protein ameloblastin (AMBN). Transgenic mice with 5-fold elevated AMBN levels in mandibles suffered from root cementum resorption, delamination, and reduced alveolar bone thickness. AMBN gain of function also resulted in a significant reduction in trabecular bone volume and bone mass dentistry in 42 days postnatal mouse jaws. In an in vitro model of osteoclastogenesis, AMBN modulated osteoclast differentiation from bone marrow derived monocytes (BMMCs), and dramatically increased osteoclast numbers and resorption pits. Furthermore, AMBN more than doubled BMMC adhesion, accelerated cell spreading, and promoted podosome belt and actin ring formation. These effects were associated with elevated ERK1/2 and AKT phosphorylation as well as higher expression of osteoclast activation related genes. Blocking integrin α2β1 and ERK 1/2 pathways alleviated the effects of AMBN on osteoclast differentiation. Together, our data indicate that AMBN increases osteoclast number and differentiation as well as mineralized tissue resorption by regulating cell adhesion and actin cytoskeleton polymerization, initiating integrin-dependent extracellular matrix signaling cascades and enhancing osteoclastogenesis.

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Funding

These studies were supported by generous funding through NIDCR grants DE18057 and DE19155 to XL.

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Publisher Statement

NOTICE: This is the author’s version of a work that was accepted for publication in BONE. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in BONE, [Vol 54, Issue 1, 2013] DOI: 10.1016/j.bone.2013.01.041

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Elsevier

Language

en_US

issn

1873-2763

Issue date

01/05/2013

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