title: Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus.
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.
authors.affiliation: Laboratory of Cell and Tissue Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan kmatsuo@keio.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Laboratory of Cell and Tissue Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Ratoc System Engineering Co., Ltd., 1-24-8 Sekiguchi, Bunkyo, Tokyo 162-0041, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Nango
authors.affiliation: Laboratory Animal Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Shimoda
authors.affiliation: Department of Vascular Biology, The Sakaguchi Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Research Center for Animal Life Science, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ema
authors.affiliation: Genes, Development and Disease Group, National Cancer Research Centre (CNIO), Cancer Cell Biology Programme, Melchor Fernandez Almagro 3, Madrid 28029, Spain.
authors.forename: Latifa
authors.initials: L
authors.lastname: Bakiri
authors.affiliation: Genes, Development and Disease Group, National Cancer Research Centre (CNIO), Cancer Cell Biology Programme, Melchor Fernandez Almagro 3, Madrid 28029, Spain.
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.affiliation: X-ray Research Laboratory, Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima, Tokyo 196-8666, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, Katahira 2-1-1, Aoba, Sendai Miyagi 980-8577, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yashiro
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, Katahira 2-1-1, Aoba, Sendai Miyagi 980-8577, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Momose
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism / Q000502:physiology*; D002356:Cartilage / Q000098:blood supply / Q000196:embryology*; D006652:Histological Techniques; D007091:Image Processing, Computer-Assisted; D008307:Malleus / Q000098:blood supply / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D017356:Synchrotrons; D014057:Tomography, X-Ray Computed; D000099169:Fos-Related Antigen 1
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D000099169:Fos-Related Antigen 1
keywords: AP-1 transcription factor; Auditory ossicle; Blood vessel; Osteogenic capillary; Synchrotron radiation