Degeneration of the osteocyte network in the C57BL/6 mouse model of aging
Open accessAbstract
Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to those in humans were observed, including increased cortical diameter, decreased cortical thickness, reduced trabecular BV/TV and cortical porosities. This was associated with a dramatic reduction in osteocyte dendrite number and cell density, particularly in females, where osteocyte dendricity decreased linearly from 5, 12, 18 to 22mo and correlated significantly with cortical bone parameters. Reduced dendricity preceded decreased osteocyte number, suggesting dendrite loss may trigger loss of viability. Age-related degeneration of osteocyte networks may impair bone anabolic responses to loading and gender differences in osteocyte cell body and lacunar fluid volumes we observed in aged mice may lead to gender-related differences in mechanosensitivity. Therapies to preserve osteocyte dendricity and viability may be beneficial for bone health in aging.
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Throughout aging, a large and linear reduction in dendrite number and cell body density directly related to the deterioration of cortical parameters has been observed.
“Throughout aging, a large and linear reduction in dendrite number and cell body density directly related to the deterioration of cortical parameters has been observed.18”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [18]
Since decreased osteocyte number accompanies reduced dendritic density, it has been suggested that dendrite loss might contribute to diminished osteocyte viability because a certain degree of locally and/or systemically triggered anabolic signaling through the osteocyte-lacunocanalicular system is lost.
“Since decreased osteocyte number accompanies reduced dendritic density, it has been suggested that dendrite loss might contribute to diminished osteocyte viability because a certain degree of locally and/or systemically triggered anabolic signaling through the osteocyte-lacunocanalicular system is lost (see below).18”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [18]
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Self-citation
- Authors
- Tiede-Lewis, L. M., Xie, Y., Hulbert, M. A., Campos, R., Dallas, M. R., Dusevich, V., Bonewald, L. F., & Dallas, S. L.
- Affiliations
- University of Missouri–Kansas City (US)
- Indiana University Indianapolis (US)
- Corresponding author
- Dallas, Mark R.
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2017-10-26
- Volume
- 9
- Issue
- 10
- Pages
- 2190-2208
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC5680562
- OpenAlex
- W2765487614
- Cited by
- 176
- References
- 58
- Citations by year
- 2026: 21 · 2025: 25 · 2024: 18 · 2023: 20 · 2022: 22 · 2021: 16 · 2020: 26 · 2019: 17 · 2018: 9 · 2015: 1
- FWCI
- 15.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion, cc-by)
- PMC
- Funders
- National Institute on Aging (P01AG039355)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR054449)
- National Center for Research Resources (S10RR027668)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Keywords
- osteocytes, age-related bone loss, cortical bone, trabecular bone, bone microarchitecture, sex differences, mechanosensitivity, C57BL/6 mice
- MeSH terms
- Aging, Animals, Bone and Bones, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Osteocytes, Osteoporosis, Mice
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