Parathyroid Hormone Remodels Bone Transitional Vessels and the Leptin Receptor-Positive Pericyte Network in Mice
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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Pericyte migration contributes to osteoprogenitor recruitment to the BRC during PTH-induced bone remodeling.
“Pericyte migration contributes to the osteoprogenitor recruitment to the BRC during PTH-induced bone remodeling.135”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [135]
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Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
Re-thinking the bone remodeling cycle mechanism and the origin of bone loss
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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
- Publisher
- Oxford University Press (OUP)
- 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
- Licence
- 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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