Decline in calcitonin receptor expression in osteocytes with age
Open accessAbstract
We have previously shown that co-administration of the transient osteoclast inhibitor, salmon calcitonin (sCT), blunts the anabolic effect of parathyroid hormone (PTH) in young rats and increases osteocytic expression of the bone formation inhibitor sclerostin ( Sost ). To determine whether this also occurs in adult animals, we co-administered sCT with PTH to 6-month-old sham-operated (SHAM) and ovariectomised (OVX) rats. While sCT reduced the stimulatory effect of PTH on serum amino-terminal propeptide of type 1 procollagen levels, in contrast to its influence in young rats, sCT did not reduce the anabolic effect of PTH on femoral bone mineral density, tibial trabecular bone volume or bone formation rate in 6-month-old SHAM or OVX rats. Quantitative real-time PCR analysis of femoral metaphyses collected 1 and 4 h after a single PTH injection confirmed a significant increase in mRNA levels for interleukin 6 ( Il6 ) and ephrinB2 ( EfnB2 ), and a significant reduction in Sost and dentin matrix protein-1 ( Dmp1 ) in response to PTH. However, in contrast to observations in young rats, these effects were not modified by co-administration of sCT, nor did sCT significantly modify Sost , Dmp1 , or matrix extracellular phosphoglycoprotein ( Mepe ) mRNA levels. Furthermore, while CT receptor (CTR) mRNA ( Calcr ) was readily detected in GFP+ osteocytes isolated from young (3-week-old) DMP1–GFP mice, Calcr levels in osteocytes declined as mice aged, reaching levels that were undetectable in long bone at 49 weeks of age. These data indicate that osteocyte-mediated responses to CT are most likely to be of physiological relevance in young rodents.
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Calcr mRNA was expressed in osteocytes isolated from 3-week-old mice, declined with age, and was undetectable at 49 weeks.
“Calcr mRNA was expressed in osteocytes isolated from 3-wk-old mice, but its level declined as mice aged and was undetectable at 49 wk of age.”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [79]
The Results report Calcr mRNA in osteocytes from 3-week-old mice and declining levels with age. At 49 weeks, however, it was undetectable in long-bone osteocytes but still detected in calvarial osteocytes; the claim omits that distinction. (LLM, conf=0.91)
Experimental — accuracy not yet measuredCalcitonin activity in osteocytes is likely to be physiologically relevant in young rodents.
“The authors concluded that the activity of calcitonin in osteocytes is likely to be physiologically relevant in young rodents (79).”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [79]
Osteocytes express specific calcitonin receptors, which are progressively lost with age.
“Osteocytes express specific calcitonin receptors, which are progressively lost with age.106”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [106]
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- Authors
- Gooi, J. H., Chia, L. Y., Walsh, N. C., Karsdal, M. A., Quinn, J. M. W., Martin, T. J., & Sims, N. A.
- Affiliations
- The University of Melbourne (AU)
- Nordic Bioscience (Denmark) (DK)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2014-02-10
- Volume
- 221
- Issue
- 2
- Pages
- 181-191
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2095622015
- Semantic Scholar
- 27eb07c5726ed5dbf28ca0b94e3886cb6fc3cb58
- Cited by
- 22
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 3
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Eli Lilly and Company
- Osteoporosis Australia
- National Health and Medical Research Council (1002730)
- 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
- calcitonin receptor, osteocytes, aging, salmon calcitonin, parathyroid hormone, sclerostin, bone formation, ovariectomy, trabecular bone volume, bone mineral density, interleukin-6, ephrin-B2, DMP1, MEPE
- MeSH terms
- Aging, Animals, Calcitonin, Cells, Cultured, Female, Mice, Transgenic, Osteocytes, Down-Regulation, Rats, Sprague-Dawley, Receptors, Calcitonin, Gene Expression Regulation, Developmental, Mice, Rats
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