Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro
Abstract
During bone resorption, osteoclasts are closely associated with endothelial cells. The latter are able to produce several agents that regulate bone resorption. In view of the increasing evidence that angiotensin II, which can be generated by endothelial cells, has actions outside the traditional renin-angiotensin system, we tested the effect of angiotensin II on bone resorption. Angiotensin II showed no effect either on osteoclast formation or on bone resorption by isolated osteoclasts. However, in co-cultures of osteoclasts with calvarial or MC3T3-E1 osteoblastic cells, and in osteoclastic cultures co-cultured with other bone cells obtained by prolonged sedimentation, angiotensin II stimulated bone resorption to a similar degree to that observed with 1,25(OH)2 vitamin D3. Stimulation of resorption was noted at concentrations of 10−7m and above. We found that angiotensin I also stimulated bone resorption in co-cultures of osteoclasts with osteoblastic cells, and that this action was inhibited by inhibitors of angiotensin-converting enzyme. These results identify angiotensin I and II as potent stimulators of osteoclastic bone resorption, and raise the possibility that bone might contain a tissue-renin-angiotensin system that might play a role in the regulation of bone resorption. Journal of Endocrinology (1997) 152, 5–10
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Angiotensin II, a major hormone of the RAAS, supports re-allocation of energy-rich fuels and calcium/phosphorus to an activated immune system.
“Thus, similar to the SNS with its major neurotransmitters noradrenaline/adrenaline, angiotensin II, a major hormone of the RAAS, supports re-allocation of energy-rich fuels and calcium/phosphorus to an activated immune system.”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [76]
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Angiotensin II accelerates osteoporosis by activating osteoclasts
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“Although previous reports showed that the receptor for Ang II is expressed in osteoblasts and osteoclasts, the effects of Ang II are controversial (8, 9).”
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Activation of Renin-Angiotensin System Induces Osteoporosis Independently of Hypertension
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“There have been several reports on the effects of AngII on bone cell function in vitro, including inhibition of osteoblastic differentiation and mineralization,((24)) stimulation of proliferation and collagen synthesis in osteoblasts,((25)) and stimulation of osteoclastic bone resorption.((22)) Hatton et al.”
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BackgroundAngiotensin II Type 2 Receptor Blockade Increases Bone Mass
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“In in vitro studies Ang II has decelerated osteoblast differentiation and mineralisation, and stimulated bone resorption [35, 36 ], one study showing the anabolic effect of Ang II in the bone formation process [37].”
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“Different components of the RAS have been found to be synthesized and to be active in osteoblasts and in osteoclasts (Hatton et al., 1997; Hiruma et al., 1997; Izu et al., 2009).”
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“There are experimental data to suggest that angiotensin II stimulates osteoclastic activities via its effects on osteoblasts [3], but it may also stimulate proliferation of osteoblasts [4].”
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“Studies have suggested that Ang II is a potent stimulator of osteoclastic bone resorption [8], and it promotes the differentiation and activation of osteoclasts indirectly via upregulating the”
BackgroundThe Interplay Between the Renin-Angiotensin-Aldosterone System and Parathyroid Hormone
Zheng, M.-H., Li, F., Xu, F., Lin, X., Wang, Y., Xu, Q.-S., Guo, B., & Yuan, L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00539 · Cited by 67 · see citing works
“Angiotensin I (Ang I), angiotensin II (Ang II), and aldosterone can effectively stimulate bone resorption of osteoclasts, causing osteolysis, thus leading to osteoporosis (4, 5).”
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“Despite these contradictory results about the receptor it activates, the importance and modulatory effect of Ang II in osteoblastic bone formation and osteoclast-mediated bone resorption is highly significant, and needs further investigation [21, 23, 26].”
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“Components of the RAS such as angiotensin-converting enzyme (ACE) and angiotensin II are found locally in several tissues [55–57] and have been found to be expressed in osteoblasts and osteoclasts [58, 59].”
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“Although the mechanism underlying the observed associations is unknown, angiotensin type I receptors are present on bone cells, and in vitro studies suggest that angiotensin I and II could stimulate bone resorption (31).”
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“The results identify angiotensin I and II as potent stimulators of osteoclastic bone resorption and speak in favor of the possibility that bones might contain a tissue renin–angiotensin system that could play a role in the regulation of bone resorption [7].”
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Vos, M. B., Natta, M. L. V., Blondet, N. M., Dasarathy, S., Fishbein, M. H., Hertel, P. M., Jain, A. K., Karpen, S. J., Lavine, J. E., Mohammad, S., et al. (2022) · Hepatology · doi:10.1002/hep.32403 · Cited by 38 · see citing works
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“Furthermore, angiotensin II has been identified as a powerful stimulator of osteoclastic bone resorption in vitro, ie, a potential foster of osteoporosis, pointing at the possibility that bone might contain a tissue– renin-angiotensin system, playing a role in the regulation of bone metabolism [ 39 ].”
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“[6] reported that both angiotensin I (Ang I) and Ang II stimulated osteoclastogenesis in osteoblast and Yanping Yang contributed equally to this work.”
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“Finally, some studies have also suggested that increased angiotensin II levels in hypertensive patients have a harmful effect by increasing bone resorption and inhibiting mineralization [10-12].”
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BackgroundResultInfluentialThe role of renin angiotensin system in the pathophysiology of rheumatoid arthritis
Moreira, F. R. C., de Oliveira, T. A., Ramos, N. E., Abreu, M. A. D., & Silva, A. C. E. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06672-8 · Cited by 25 · see citing works
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Angiotensin II reduces calcium uptake into bone
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Aging and “Age-Related” Diseases - What Is the Relation?
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“Key components of the tissue-based RAAS, including ACE/Ang II/AT-1R, are also synthesized and active in bone cells, osteoblasts and osteoclasts [296] and human and animal synovial tissue, and their expression levels correlate with the degree of synovial inflammation and the severity of arthritis…”
Locally Administrated Perindopril Improves Healing in an Ovariectomized Rat Tibial Osteotomy Model
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“Previous studies have indicated that different components of the RAS have been found to be synthesized and active in osteoblasts and osteoclasts [11,12,13].”
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“It has been shown to be a potent stimulator of osteoclastic bone resorption[4,6] and to decrease”
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“Among the inhibiting factors, Ang II is a potent stimulator of osteoclastic bone resorption (11), and it promotes the differentiation and activation of osteoclasts indirectly via upregulating the expression of RANKL by binding to different receptors in osteoblasts.”
Non-canonical signalling and roles of the vasoactive peptides angiotensins and kinins
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“[19] indicated that Ang II was a potent stimulator of osteoclastic bone resorption.”
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Systemic Treatment with Telmisartan Improves Femur Fracture Healing in Mice
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BackgroundTissue Renin-Angiotensin System in the Intervertebral Disc
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“RAS is associated with bone metabolism and Ang II is a potent stimulator of osteoclastogenesis [16, 34].”
BackgroundBone healing of mandibular critical-size defects in spontaneously hypertensive rats
Chin, V. K. L., Shinagawa, A., & Naclério‐Homem, M. D. G. (2013) · Brazilian Oral Research · doi:10.1590/s1806-83242013000500006 · Cited by 14 · see citing works
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“Multinucleated cells of the monocyte/macrophage lineage, which can also be angiotensin II targets, are the source of osteoclasts [53].”
BackgroundACE-inhibitors: a preventive measure for bone flap resorption after autologous cranioplasty?
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“Both Ang I and II have been identified to stimulate osteo-clastogenesis in osteoblast and osteoclast co-cultures, which was inhibited by treatment with an Ang-converting enzyme (ACE) inhibitor (8).”
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“However, in coculture of osteoclasts with osteoblasts ang II stimulates the bone resorption.([7])”
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“The other bone cell functions of Ang-II include inhibition of osteoblastic differentiation, collagen synthesis in osteoblasts and resorption of bone matrix by the osteoclasts (25).”
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“Ang II stimulated bone resorption in cocultures of osteoclasts with osteoblastic cells [62].”
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The challenge to make fuller use of our knowledge about children.
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“Main components of tissue-based RAAS, including ACE/Ang II/AT-1R have been found to be synthesized and active in bone cells, osteoblasts and osteoclasts [13, 15].”
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“The octapeptide angiotensin II (AngII) generated from the inactive dectapeptide angiotensin I (AngI) by the cleavage action of angiotensin converting enzymes (ACE) was found to regulate bone metabolism and remodeling through angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) that were found to be located…”
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“Ang II is a potent stimulator of osteoclastic bone resorption (12,13).”
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Bone Homeostasis: An Emerging Role for the Renin-Angiotensin System
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“These findings suggest that bone may have a tissue RAS that could regulate bone resorption and recognize Ang I and Ang II as strong osteoclastic bone resorption inducers (Hatton et al. 1997; Haznedaroglu and Oztürk 2003).”
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“Moreover, the effector octapeptide (AngII) was found in osteoblasts and osteoclasts [5], which may be involved in attenuating osteoblasts differentiation [6] and aggravating the oste-oclastic activity, by stimulating the receptor activator nuclear factor kappa-B ligand (RANKL) [7].”
Background
- Authors
- Hatton, R., Stimpel, M., & Chambers, T. J.
- Affiliations
- St George's Hospital (GB)
- ORCID
- Chambers, T J
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 1997-01-01
- Volume
- 152
- Issue
- 1
- Pages
- 5-10
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2021400723
- Cited by
- 133
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 10 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 10 · 2016: 2 · 2015: 6 · 2014: 12 · 2013: 5 · 2012: 8
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- angiotensin II, angiotensin I, osteoclast resorption, renin-angiotensin system, bone cells, osteoblasts, osteoclasts, ACE inhibitors, 1,25-dihydroxyvitamin D3, tissue renin-angiotensin system, co-culture
- MeSH terms
- Angiotensin I, Angiotensin II, Animals, Bone Resorption, Cattle, Cells, Cultured, Dose-Response Relationship, Drug, Mice, Inbred CBA, Osteoblasts, Osteoclasts, Stimulation, Chemical, Rats, Wistar, Coculture Techniques, Mice, Rats
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