Angiotensin II Stimulates the Proliferation of Osteoblast-Rich Populations of Cells from Rat Calvariae

Hiruma, Yoshiharu; Inoue, Atsuto; Hirose, Shigehisa; Hagiwara, Hiromi

doi:10.1006/bbrc.1996.5914

Cited by 77 publications

(71 citation statements)

References 12 publications

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“…A mechanism that could partially explain our histometric results may also be attributed to the influence of angiotensin II on bone cells. Although the effect of angiotensin II on osteoblastic cells is still controversial and predominantly based on in vitro studies, [23][24][25] there is some evidence to suggest that this mediator is a potent suppressor of the differentiation of osteoblastic cells and, consequently, of the bone formation by these cells. 22 Our findings are contradictory to those described by Pereira et al (2007), 15 in which the amount of newly-formed bone was similar in SHR and NTR animals at 7 days and higher in SHR at 21 days post-operative.…”

Section: Discussionmentioning

confidence: 99%

Trabecular bone area and bone healing in spontaneously hypertensive rats: a histometric study

et al. 2010

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Abstract:Clinical and experimental studies have demonstrated some negative effect of hypertension on bone mineral density. The aim of this study was to evaluate bone healing and trabecular bone area (TBA) in spontaneously hypertensive rats (SHR), a well-established model of essential hypertension, when compared to normotensive rats (NTR). A critical-size defect was surgically created in the right tibia of SHR (n = 12) and normotensive rats (NTR; n = 12), while the contralateral tibia was left intact. Eight days later, the animals were sacrificed and the specimens processed in order to obtain decalcified sections. The area of newly-formed bone (NB) within the defect of the right tibia and the TBA in the left tibia were histometrically evaluated. At 8 days post-operative, SHR presented a significantly smaller area of NB when compared to NTR (p < 0.05). In addition, SHR demonstrated a lower TBA than NTR group. In conclusion, the present study demonstrated that SHR rats presented a disturbed bone healing and reduced TBA.

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Section: Discussionmentioning

confidence: 99%

Trabecular bone area and bone healing in spontaneously hypertensive rats: a histometric study

et al. 2010

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“…Ang II stimulates proliferation and decreases the ALP activity of rat calvarial cells. [33][34][35] These effects were antagonized by AT1 antagonist, indicating that the effect of Ang II was mediated through AT1 receptors. Therefore, it is conceivable that agents that interfere RAS might affect bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35] Since AT1 antagonists disturb the signaling of Ang II by inhibiting its binding to the AT1 receptor, it is expected that these drugs may have a similar effect to ACE inhibitors on bone metabolism in vivo. In our study, AT1 antagonists TCV-116 and KW-3433 did not change either ALP activity or DNA content of MC3T3-E1, implying that these classes of drugs have no direct effect on osteoblast differentiation and proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, Ang II promotes cell growth and inhibits differentiation of osteoblast, and these effects have been shown to be mediated through AT1. [33][34][35] An AT1 antagonist, DuP 753, itself is reported to have no effect on ALP activity of rat calvarial osteoblast 34) ; * To whom correspondence should be addressed. e-mail: ssugimoto@kyowa.co.jp © 2001 Pharmaceutical Society of Japan…”

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Effects of Various Antihypertensive Drugs on the Function of Osteoblast.

Nishiya

Sugimoto

2001

Biological & Pharmaceutical Bulletin

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Several studies have suggested that high blood pressure is associated with abnormalities in calcium metabolism, leading to increased calcium loss, secondary activation of the parathyroid gland, and increased removal of calcium from bone. [1][2][3][4][5][6][7] Consistently, studies in hypertensive rats have shown that hypercalciuria and ensuing hyperparathyroidism lead to reduced growth and detectable decrease in total bonemineral content later in life. 8,9) Recently, it was also shown that higher blood pressure in elderly white women is statistically associated with increased bone loss at the femoral neck, which may contribute to bone fracture. 10) Drugs used as primary choice for the treatment of hypertension include calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor type1 (AT1) antagonists, diuretics, b-blockers, and a-blockers. 11) The first three drugs are especially widely used in Japan. The mechanism by which each drug lowers blood pressure differs. Calcium channel blockers primarily inhibit calcium influx through the L-type voltage-dependent calcium channel at the level of vascular smooth muscle, thereby disrupting the excitation contraction process. 12,13) Both ACE inhibitors and AT1 antagonists interfere with the renin-angiotensin system (RAS). The former inactivates the conversion of angiotensin I into angiotensin II (Ang II), which is a vasoconstrictive peptide, while the latter blocks the binding of Ang II to its receptor. 14,15) Osteoblasts are derived from mesenchymal stem cells and play a pivotal role in bone formation. During differentiation, they first express type I collagen, then alkaline phosphatase (ALP), and other bone matrix proteins and finally form mineralized bone. Osteoblasts express voltage-dependent calcium channels. 16) Various bone regulatory factors such as vitamin D 3 , [17][18][19] parathyroid hormone, 17,20,21) and prostaglandin E 2 17,22) cause a rise in intracellular calcium concentration ([Ca 2ϩ ] i ), at least part of which is decreased by dihydropyridine-type calcium channel blockers. These factors also promote or inhibit osteoblast differentiation. [23][24][25][26] Thus, it is suggested that signaling through the L-type calcium channel may be important for osteoblast functions. However, the fact that these factors give rise to multiple signals independent of calcium influx (i.e., transcription of specific genes, 27) cAMP production, 20,28) release of calcium ion from intracellular store 17) ) obscures the role of L-type calcium channel. Recently, Kosaka and Uchii found that a calcium channel blocker benidipine, but not amlodipine or nifedipine, increased ALP activity of osteoblastic cells isolated from neonatal mouse calvaria. 29) We further investigated the effects of benidipine on osteoblastic functions using osteoblastic cell line MC3T3-E1, 30) which is widely used in studies on various aspects of osteoblast differentiation since it expresses osteoblast markers and forms a mineralized extracellular matrix. 31,32) There we ...

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“…Renin angiotensin system (RAS) is operating not only systemically but also locally in several tissues, and bone microenvironments have been studied in this regard (15,16). Osteoblasts and osteoclasts express angiotensin II type 1 receptor in cell cultures (17)(18)(19), suggesting the existence of local RAS in bone. However, whether RAS components are expressed in bone in vivo is not known.…”

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confidence: 99%

Angiotensin II Type 2 Receptor Blockade Increases Bone Mass

Izu

Mizoguchi

Kawamata

et al. 2009

Journal of Biological Chemistry

111

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Renin angiotensin system (RAS) regulates circulating blood volume and blood pressure systemically, whereas RAS also plays a role in the local milieu. Previous in vitro studies suggested that RAS may be involved in the regulation of bone cells. However, it was not known whether molecules involved in RAS are present in bone in vivo. In this study, we examined the presence of RAS components in adult bone and the effects of angiotensin II type 2 (AT2) receptor blocker on bone mass. Immunohistochemistry revealed that AT2 receptor protein was expressed in both osteoblasts and osteoclasts. In addition, renin and angiotensin II-converting enzyme were expressed in bone cells in vivo. Treatment with AT2 receptor blocker significantly enhanced the levels of bone mass, and this effect was based on the enhancement of osteoblastic activity as well as the suppression of osteoclastic activity in vivo. These results indicate that RAS components are present in adult bone and that blockade of AT2 receptor results in alteration in bone mass.Osteoporosis is one of the major diseases associated with aging. This disease is based on the imbalance between the two major activities, i.e. bone formation and bone resorption. Systemic signals such as parathyroid hormone (PTH) 3 and vitamin D are the major regulators of the maintenance of bone mass and blood calcium (1-3). In addition, bone mass levels are also determined by a central nervous control through the activities of sympathetic tone on both bone formation and resorption sides (4 -7). In the local milieu of bone, two major types of cells, osteoblasts and osteoclasts, are located in close proximity, exchange their signals, and coordinately resorb and form bone matrix (8). Such events are controlled by molecules present in the local microenvironment. These include cytokines, their modulators, and matrix proteins secreted by osteoblasts and osteoclasts (9 -11). However, the bone environment is quite heterogeneous, and there are also cells other than these two types. Microvasculatures are serving as a root to supply osteoclast progenitors, which are derived from hematopoietic lineage cells. Vasculatures in bone are also considered to give rise to progenitors for osteoblastic cells from their perivascular regions (12). In addition to the anatomical relationship between the vascular cells and bone cells, these cells may be functionally involved in the coordinate regulation of bone mass.Recent clinical studies indicated that beta blockers and antihypertension drugs would reduce the risk of bone fractures in the elderly populations (13,14). This suggests a possible link between vascular and skeletal systems. Renin angiotensin system (RAS) is operating not only systemically but also locally in several tissues, and bone microenvironments have been studied in this regard (15,16). Osteoblasts and osteoclasts express angiotensin II type 1 receptor in cell cultures (17-19), suggesting the existence of local RAS in bone. However, whether RAS components are expressed in bone in vivo is not known.A...

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Angiotensin II Stimulates the Proliferation of Osteoblast-Rich Populations of Cells from Rat Calvariae

Cited by 77 publications

References 12 publications

Trabecular bone area and bone healing in spontaneously hypertensive rats: a histometric study

Trabecular bone area and bone healing in spontaneously hypertensive rats: a histometric study

Effects of Various Antihypertensive Drugs on the Function of Osteoblast.

Angiotensin II Type 2 Receptor Blockade Increases Bone Mass

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