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Development. 2015 Nov 15;142(22):3912-20. doi: 10.1242/dev.123885. Epub 2015 Oct 1.

Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus.

Author information

1
Laboratory of Cell and Tissue Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan kmatsuo@keio.jp.
2
Laboratory of Cell and Tissue Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
3
Ratoc System Engineering Co., Ltd., 1-24-8 Sekiguchi, Bunkyo, Tokyo 162-0041, Japan.
4
Laboratory Animal Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
5
Department of Vascular Biology, The Sakaguchi Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
6
Research Center for Animal Life Science, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
7
Genes, Development and Disease Group, National Cancer Research Centre (CNIO), Cancer Cell Biology Programme, Melchor Fernandez Almagro 3, Madrid 28029, Spain.
8
X-ray Research Laboratory, Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima, Tokyo 196-8666, Japan.
9
Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, Katahira 2-1-1, Aoba, Sendai Miyagi 980-8577, Japan.

Abstract

Endochondral ossification is a developmental process by which cartilage is replaced by bone. Terminally differentiated hypertrophic chondrocytes are calcified, vascularized, and removed by chondroclasts before bone matrix is laid down by osteoblasts. In mammals, the malleus is one of three auditory ossicles that transmit vibrations of the tympanic membrane to the inner ear. The malleus is formed from a cartilaginous precursor without growth plate involvement, but little is known about how bones of this type undergo endochondral ossification. Here, we demonstrate that in the processus brevis of the malleus, clusters of osteoblasts surrounding the capillary loop produce bone matrix, causing the volume of the capillary lumen to decrease rapidly in post-weaning mice. Synchrotron X-ray tomographic microscopy revealed a concentric, cylindrical arrangement of osteocyte lacunae along capillaries, indicative of pericapillary bone formation. Moreover, we report that overexpression of Fosl1, which encodes a component of the AP-1 transcription factor complex, in osteoblasts significantly blocked malleal capillary narrowing. These data suggest that osteoblast/endothelial cell interactions control growth plate-free endochondral ossification through 'osteogenic capillaries' in a Fosl1-regulated manner.

KEYWORDS:

AP-1 transcription factor; Auditory ossicle; Blood vessel; Osteogenic capillary; Synchrotron radiation

PMID:
26428006
PMCID:
PMC4712877
DOI:
10.1242/dev.123885
[Indexed for MEDLINE]
Free PMC Article

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