Parathyroid hormone hormone-related protein and the PTH receptor regulate angiogenesis of the skin

A. Godwin Diamond, Ryan M. Gonterman, Aileen L. Anderson, Keshav Menon, Carlos D. Offutt, Chad H. Weaver, William M. Philbrick, John Foley

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

In developing organs, parathyroid hormone (PTH)/parathyroid hormone-related protein (PTHrP) receptor (PPR) signaling inhibits proliferation and differentiation of mesenchyme-derived cell types resulting in control of morphogenic events. Previous studies using PPR agonists and antagonists as well as transgenic overexpression of the PPR ligand PTHrP have suggested that this ligand receptor combination might regulate the anagen to catagen transition of the hair cycle. To further understand the precise role of PTHrP and the PPR in the hair cycle, we have evaluated hair growth in the traditional K14-PTHrP (KrP) and an inducible bitransgenic PTHrP mice. High levels of PTHrP trangene expression limited to the adult hair cycle resulted in the production of shorter hair shafts. Morphometric analysis indicated that reduced proliferation in the matrix preceded the appearance of thinner hair follicles and shafts during late anagen. CD31 staining revealed that the late anagen hair follicles of the KrP mice were surrounded by reduced numbers of smaller diameter capillaries as compared to controls. Moreover, the fetal skins of the PTHrP and PPR knockouts (KOs) had reciprocal increases in the length, diameter, and density of capillaries. Finally, crossing the KrP transgene onto a thrombospondin-1 KO background reversed the vascular changes as well as the delayed catagen exhibited by these mice. Taken together, these findings suggest that PTHrP's influence on the hair cycle is mediated in part by its effects on angiogenesis.

Original languageEnglish
Pages (from-to)2127-2134
Number of pages8
JournalJournal of Investigative Dermatology
Volume126
Issue number9
DOIs
StatePublished - Sep 2006

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Parathyroid Hormone Receptor Type 1
Parathyroid Hormone-Related Protein
Hormones
Parathyroid Hormone
Skin
Proteins
Hair
Hair Follicle
Ligands
Thrombospondin 1
Mesoderm
Transgenes
Blood Vessels

ASJC Scopus subject areas

  • Dermatology

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Parathyroid hormone hormone-related protein and the PTH receptor regulate angiogenesis of the skin. / Diamond, A. Godwin; Gonterman, Ryan M.; Anderson, Aileen L.; Menon, Keshav; Offutt, Carlos D.; Weaver, Chad H.; Philbrick, William M.; Foley, John.

In: Journal of Investigative Dermatology, Vol. 126, No. 9, 09.2006, p. 2127-2134.

Research output: Contribution to journalArticle

Diamond, AG, Gonterman, RM, Anderson, AL, Menon, K, Offutt, CD, Weaver, CH, Philbrick, WM & Foley, J 2006, 'Parathyroid hormone hormone-related protein and the PTH receptor regulate angiogenesis of the skin', Journal of Investigative Dermatology, vol. 126, no. 9, pp. 2127-2134. https://doi.org/10.1038/sj.jid.5700338
Diamond, A. Godwin ; Gonterman, Ryan M. ; Anderson, Aileen L. ; Menon, Keshav ; Offutt, Carlos D. ; Weaver, Chad H. ; Philbrick, William M. ; Foley, John. / Parathyroid hormone hormone-related protein and the PTH receptor regulate angiogenesis of the skin. In: Journal of Investigative Dermatology. 2006 ; Vol. 126, No. 9. pp. 2127-2134.
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