Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus

Koichi Matsuo, Yukiko Kuroda, Nobuhito Nango, Kouji Shimoda, Yoshiaki Kubota, Masatsugu Ema, Latifa Bakiri, Erwin F. Wagner, Yoshihiro Takeda, Wataru Yashiro, Atsushi Momose

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)3912-3920
Number of pages9
JournalDevelopment (Cambridge)
Issue number22
Publication statusPublished - 2015 Nov 15


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

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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