Journal article
Crosstalk between senescent bone cells and the bone tissue microenvironment influences bone fragility during chronological age and in diabetes
- Abstract:
- Bone is a complex organ serving roles in skeletal support and movement, and is a source of blood cells including adaptive and innate immune cells. Structural and functional integrity is maintained through a balance between bone synthesis and bone degradation, dependent in part on mechanical loading but also on signaling and influences of the tissue microenvironment. Bone structure and the extracellular bone milieu change with age, predisposing to osteoporosis and increased fracture risk, and this is exacerbated in patients with diabetes. Such changes can include loss of bone mineral density, deterioration in micro-architecture, as well as decreased bone flexibility, through alteration of proteinaceous bone support structures, and accumulation of senescent cells. Senescence is a state of proliferation arrest accompanied by marked morphological and metabolic changes. It is driven by cellular stress and serves an important acute tumor suppressive mechanism when followed by immune-mediated senescent cell clearance. However, aging and pathological conditions including diabetes are associated with accumulation of senescent cells that generate a pro-inflammatory and tissue-destructive secretome (the SASP). The SASP impinges on the tissue microenvironment with detrimental local and systemic consequences; senescent cells are thought to contribute to the multimorbidity associated with advanced chronological age. Here, we assess factors that promote bone fragility, in the context both of chronological aging and accelerated aging in progeroid syndromes and in diabetes, including senescence-dependent alterations in the bone tissue microenvironment, and glycation changes to the tissue microenvironment that stimulate RAGE signaling, a process that is accelerated in diabetic patients. Finally, we discuss therapeutic interventions targeting RAGE signaling and cell senescence that show promise in improving bone health in older people and those living with diabetes.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.8MB, Terms of use)
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- Publisher copy:
- 10.3389/fphys.2022.812157
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Physiology More from this journal
- Volume:
- 13
- Article number:
- 812157
- Publication date:
- 2022-03-21
- Acceptance date:
- 2022-01-27
- DOI:
- EISSN:
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1664-042X
- Language:
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English
- Keywords:
- Pubs id:
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1249671
- Local pid:
-
pubs:1249671
- Deposit date:
-
2022-04-07
- ARK identifier:
Terms of use
- Copyright holder:
- Teissier et al.
- Copyright date:
- 2022
- Rights statement:
- ©2022 Teissier, Temkin, Pollak and Cox. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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