Directed glia-assisted angiogenesis in a mature neurosensory structure: Pericytes mediate an adaptive response in human dental pulp that maintains blood-barrier function.

Summary of "Directed glia-assisted angiogenesis in a mature neurosensory structure: Pericytes mediate an adaptive response in human dental pulp that maintains blood-barrier function."

The specialized tightly controlled microcirculation of craniofacial neurosensory organs is an essential evolutionary adaptation and yet a dilemma where angiogenic remodelling occurs. Despite extreme plasticity of neurosensory structures, the capacity to reconcile barrier phenotype of the microcirculation with an angiogenic cascade, is not known. Here, we provide primary evidence for such a response in an elemental neurosensory structure, human dental pulp, following chronic carious insult. In response to hypoxic challenge neurosensory odontoblasts express hypoxia-inducible factor-1α and notch-1. Associated radial re-arrangement of astrocyte-like telacytes that communicate through a cell poor zone with the microvasculature, is observed. Activated pericytes characterised by expression of α-smooth muscle actin, are located adjacent to the telacyte attachment to the vasculature. In this location, endothelial expression of sonic hedgehog parallels expression of notch-1 by pericytes. The angiogenic response is initiated by pericyte contraction and altered endothelial polarity and proliferation leading to intussusception of endothelial cells and extensive remodelling of basement membrane with up-regulation of laminin-8 and laminin-5. These responses guide intravascular loop formation that maintains both intact basement membrane and tight junctions. This initial phase is followed by formation of anastomoses that enhance the hemodynamic capacity of the intravascular loops. The formation of anastomoses is mediated by extension of cytonemes from pericytes guided by MHC-II(+) /CD 163(+) microglia aligned with the telacytes. The cytonemes seek out pericytes on adjacent intravascular loops to initiate migration of endothelial cells. These findings support a new paradigm for understanding angiogenic capacity of neurosensory structures and aberrations of this response manifest as neuro-vasculopathies. J. Comp. Neurol., 2012. © 2012 Wiley Periodicals, Inc.

Affiliation

Institute of Dental Research, Westmead Millennium Institute and Westmead Centre for Oral Health; Department of Basic Sciences, Faculty of Dentistry, University of Sydney. rmos4386@uni.sydney.edu.au.

Journal Details

This article was published in the following journal.

Name: The Journal of comparative neurology
ISSN: 1096-9861
Pages:

Links

• PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22678627
• DOI: http://dx.doi.org/10.1002/cne.23162