The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Parathyroid Hormone (PTH)/PTH-related Peptide Type 1 Receptor (PPR) Signaling in Osteocytes Regulates Anabolic and Catabolic Skeletal Responses to PTH
Open accessAbstract
Parathyroid hormone (PTH) is the only Food and Drug Administration-approved anabolic agent to treat osteoporosis; however, the cellular targets of PTH action in bone remain controversial. PTH modulates bone turnover by binding to the PTH/PTH-related peptide (PTHrP) type 1 receptor (PPR), a G-protein-coupled receptor highly expressed in bone and kidneys. Osteocytes, the most abundant cells in adult bone, also express PPR. However, the physiological relevance of PPR signaling in osteocytes remains to be elucidated. Toward this goal, we generated mice with PPR deletion in osteocytes (Ocy-PPRKO). Skeletal analysis of these mice revealed a significant increase in bone mineral density and trabecular and cortical bone parameters. Osteoblast activities were reduced in these animals, as demonstrated by decreased collagen type I α1 mRNA and receptor activator of NF-κB ligand (RANKL) expression. Importantly, when subjected to an anabolic or catabolic PTH regimen, Ocy-PPRKO animals demonstrated blunted skeletal responses. PTH failed to suppress SOST /Sclerostin or induce RANKL expression in Ocy-PPRKO animals compared with controls. In vitro , osteoclastogenesis was significantly impaired in Ocy-PPRKO upon PTH administration, indicating that osteocytes control osteoclast formation through a PPR-mediated mechanism. Taken together, these data indicate that PPR signaling in osteocytes is required for bone remodeling, and receptor signaling in osteocytes is needed for anabolic and catabolic skeletal responses. Background: Osteocytes, the most abundant cells in adult bone, express PPR. Results: Mice with constitutive PPR deletion in osteocytes demonstrate blunted anabolic and catabolic bone responses and the inability to recruit osteoblasts and osteoclasts upon PTH administration. Conclusion: PPR in osteocytes is needed for a full skeletal response to PTH administration. Significance: PPR signaling in osteocytes is necessary for PTH-driven anabolic effects during osteoporosis therapy.
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“In contrast, when PTHR1 is deleted, RANKL release and subsequent osteoclastogenesis do not occur.81”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [81]
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Parathyroid hormone: anabolic and catabolic actions on the skeleton
Silva, B. C. C., & Bilezikian, J. P. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.03.005 · Cited by 564
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
Role and mechanism of action of sclerostin in bone
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The osteocyte as a signaling cell
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Metadata
- Authors
- Saini, V., Marengi, D. A., Barry, K. J., Fulzele, K. S., Heiden, E., Liu, X., Dedic, C., Maeda, A., Lotinun, S., Baron, R., & Pajevic, P. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Pajevic, Paola Divieti
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 288
- Issue
- 28
- Pages
- 20122-20134
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3711281
- OpenAlex
- W2035856790
- Cited by
- 167
- References
- 31
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 19 · 2019: 13 · 2018: 16 · 2017: 14 · 2016: 17 · 2015: 27 · 2014: 16 · 2013: 2
- FWCI
- 9.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- Tokyo Medical and Dental University
- National Institutes of Health (DK079161)
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK079161, R01DK079161, DK079161)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060221)
- 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
- parathyroid hormone, osteocytes, bone remodeling, osteoporosis treatment, osteoblast recruitment, osteoclastogenesis, RANKL, sclerostin, bone mineral density
- MeSH terms
- Collagen Type I, alpha 1 Chain, Animals, Body Weight, Bone and Bones, Cells, Cultured, Female, Immunohistochemistry, Male, Osteoclasts, Osteocytes, Parathyroid Hormone, Signal Transduction, Bone Density, Gene Expression, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Collagen Type I, Receptor, Parathyroid Hormone, Type 1, Mice, Osteoprotegerin, RANK Ligand
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