Cited by 27Bone Metabolism and DiseasesBone health and osteoporosis researchParathyroid Disorders and Treatments

Parathyroid Hormone Remodels Bone Transitional Vessels and the Leptin Receptor-Positive Pericyte Network in Mice

Caire, Robin, Roche, Bernard, Picot, Tiphanie, Aanei, Carmen-Mariana, He, Zhiguo, Campos, Lydia, Thomas, Mireille, Malaval, Luc +2 more·2019·Journal of Bone and Mineral Research

Abstract

Intermittent parathyroid hormone (iPTH) is anti-osteoporotic and affects bone vessels. Transitional capillaries close to the bone surface, which express both endomucin (Edm) and CD31, bear leptin receptor-expressing (LepR) perivascular cells that may differentiate into osteoblasts. Increased numbers of type H endothelial cells (THEC; ie, Edmhi/CD31hi cells assessed by flow cytometry, FACS) are associated with higher bone formation in young mice. We hypothesized that iPTH administration impacts transitional vessels by expanding THECs. Four-month-old C57/Bl6J female mice were injected with PTH 1–84 (100 μg/kg/d) or saline (CT) for 7 or 14 days. We quantified LepR+, CD31+, Edm+ cells and THECs by FACS in hindlimb bone marrow, and Edm/LepR double immunolabelings on tibia cryosections. Additionally, we analyzed bone mRNA expression of 87 angiogenesis-related genes in mice treated with either intermittent or continuous PTH (iPTH/cPTH) or saline (CT) for 7, 14, and 28 days. iPTH dramatically decreased the percentage of THECs by 78% and 90% at days 7 and 14, respectively, and of LepR+ cells at day 14 (–46%) versus CT. Immunolabeling quantification showed that the intracortical Edm+-vessel density increased at day 14 under iPTH. In the bone marrow, perivascular LepR+ cells, connected to each other via a dendrite network, were sparser under iPTH at day 14 (–58%) versus CT. iPTH decreased LepR+ cell coverage of transitional vessels only (–51%), whereas the number of LepR+ cells not attached to vessels increased in the endocortical area only (+ 49%). Transcriptomic analyses showed that iPTH consistently upregulated PEDF, Collagen-18α1, and TIMP-1 mRNA expression compared with CT and cPTH. Finally, iPTH increased immunolabeling of endostatin, a Collagen-18 domain that can be cleaved and become antiangiogenic, in both endocortical (79%) and peritrabecular transitional microvessels at day 14. Our results show that iPTH specifically remodels transitional vessels and suggest that it promotes LepR+ cell mobilization from these vessels close to the bone surface. © 2019 American Society for Bone and Mineral Research. Abstract

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Crossref · 10.1002/jbmr.3728

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Authors
Caire, R., Roche, B., Picot, T., Aanei, C.-M., He, Z., Campos, L., Thomas, M., Malaval, L., Vico, L., & Lafage-Proust, M.-H.
Affiliations
  • Inserm (FR)
  • Centre Hospitalier Universitaire de Saint-Étienne (FR)
  • BiiGC, Université de Lyon, Saint-Etienne France
  • INSERM U1059-SAINBIOSE, Université de Lyon, Saint-Etienne France
Venue
Journal of Bone and Mineral Research
Published
2019-03-28
Volume
34
Issue
8
Pages
1487-1501
ISSN
  • 0884-0431 (ISSN-L)
  • 1523-4681
OpenAlex
W2927412502
Cited by
27
References
46
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 1
FWCI
1.08
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Bone and Mineral Research (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
Keywords
bone microvasculature, pericytes, leptin receptor, endomucin, endostatin, angiogenesis, bone formation, bone marrow, osteogenic differentiation, anti-angiogenic factors, pigment epithelium-derived factor, TIMP-1
MeSH terms
Animals, Bone and Bones, Female, Gene Expression Regulation, Parathyroid Hormone, Neovascularization, Physiologic, Pericytes, Mice, Receptors, Leptin

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