Captopril alleviates glucocorticoid-induced osteonecrosis of the femoral head by mediating the ACE2/ Ang-(1-7)/Mas receptor cascade

Liu, Xiaohui; Sun, Yating; Wei, Qilu; Jiang, Wuqiang; Jiao, Ming; Yan, Junteng; Tian, Run; Yang, Pei; Wang, Kunzheng; Wang, Chunsheng

doi:10.1016/j.ejphar.2022.174871

Cited by 3 publications

(6 citation statements)

References 32 publications

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“…ACE inhibitors have been widely used in the treatment of hypertension and are the first drugs of interest to focus on the effects of RAAS inhibitors on bone metabolism. Numerous animal experiments 11,[13][14][15][16][17] and clinical studies 9,[18][19][20][21][22][23][24][25] have shown that ACE inhibitors reduce bone loss, improve BMD, increase bone biomechanical strength, reduce fracture risk, and accelerate fracture healing.…”

Section: Ace Inhibitorsmentioning

confidence: 99%

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism

Zhang,

Yin,

Yang

et al. 2023

Hypertension

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Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred antihypertensive treatment. Therefore, antihypertensive drugs have become some of the most commonly prescribed drugs in healthcare settings. However, antihypertensive drugs have different effects on bone metabolism. The results of animal and clinical studies on the effects of antihypertensive drugs on osteoporosis or fracture risk are controversial and have aroused widespread concern among clinicians. Recent studies found that angiotensin receptor blockers, selective β-adrenergic receptor blockers, and thiazide diuretics might improve bone trabecular number and bone mineral density by stimulating osteoblast differentiation, reducing osteoclast generation, and other mechanism. Furthermore, nonselective β-adrenergic receptor blockers and dihydropyridine calcium channel blockers were found to have no significant relationship with bone mineral density or bone strength, and α-adrenergic receptor blockers and loop diuretics might increase fracture risk by decreasing bone mineral density. This article aimed to review previous animal experiments, clinical studies, and meta-analyses focusing on the effects of different antihypertensive drugs on bone metabolism, and to provide a new approach for the prevention and treatment of osteoporosis.

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Section: Ace Inhibitorsmentioning

confidence: 99%

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism

Zhang,

Yin,

Yang

et al. 2023

Hypertension

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“…Furthermore, the 1,25(OH)2D-VDR interaction is impaired in T2D, further reducing bone formation and mineralization [73]. PTH, 1,25(OH) 2 D, Ang II, glucocorticoids and proinflammatory cytokines have been evidenced to cause osteoclastogenesis, leading to bone remodeling through the expression of nuclear factor-κB ligand (RANKL) [74][75][76][77]. The differentiation and bone-resorbing abilities of the osteoclast depend on RANKL and its receptor, nuclear factor-B (RANK) [77].…”

Section: Vitamin D3mentioning

confidence: 99%

“…However, the ACE2/Ang 1-7/MasR receptor arm of bone RAAS has been demonstrated to increase the expression of OPG, a glycoprotein that regulates bone remodeling [13]. OPG regulates bone remodeling by controlling osteoclast activity, hence interfering with the interaction between RANK and its ligand RANKL [76]. In order to regulate cell proliferation, the apoptosis regulator gene RANKL interacts with OPG, a ligand for the RANK receptor, under physiological conditions (Figure 4) [76].…”

Section: Ang II Upregulates Sost Gene Expressionmentioning

confidence: 99%

“…OPG regulates bone remodeling by controlling osteoclast activity, hence interfering with the interaction between RANK and its ligand RANKL [76]. In order to regulate cell proliferation, the apoptosis regulator gene RANKL interacts with OPG, a ligand for the RANK receptor, under physiological conditions (Figure 4) [76]. However, the ACE/Ang II/AT1R axis is upregulated and the ACE2/Ang 1-7/MasR arm is downregulated in T2D, consequently decreasing the expression of OPG protein [13,117].…”

Section: Ang II Upregulates Sost Gene Expressionmentioning

confidence: 99%

“…with the interaction between RANK and its ligand RANKL [76]. In order to regulate cell proliferation, the apoptosis regulator gene RANKL interacts with OPG, a ligand for the RANK receptor, under physiological conditions (Figure 4) [76].…”

Section: Ang II Upregulates Sost Gene Expressionmentioning

confidence: 99%

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The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

Mkhize

Mosili

Ngubane

et al. 2023

IJMS

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Type 2 diabetes (T2D) is associated with a plethora of comorbidities, including osteoporosis, which occurs due to an imbalance between bone resorption and formation. Numerous mechanisms have been explored to understand this association, including the renin–angiotensin–aldosterone system (RAAS). An upregulated RAAS has been positively correlated with T2D and estrogen deficiency in comorbidities such as osteoporosis in humans and experimental studies. Therefore, research has focused on these associations in order to find ways to improve glucose handling, osteoporosis and the downstream effects of estrogen deficiency. Upregulation of RAAS may alter the bone microenvironment by altering the bone marrow inflammatory status by shifting the osteoprotegerin (OPG)/nuclear factor kappa-Β ligand (RANKL) ratio. The angiotensin-converting-enzyme/angiotensin II/Angiotensin II type 1 receptor (ACE/Ang II/AT1R) has been evidenced to promote osteoclastogenesis and decrease osteoblast formation and differentiation. ACE/Ang II/AT1R inhibits the wingless-related integration site (Wnt)/β-catenin pathway, which is integral in bone formation. While a lot of literature exists on the effects of RAAS and osteoporosis on T2D, the work is yet to be consolidated. Therefore, this review looks at RAAS activity in relation to osteoporosis and T2D. This review also highlights the relationship between RAAS activity, osteoporosis and estrogen deficiency in T2D.

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Exogenous Angiotensin-(1–7) Provides Protection Against Inflammatory Bone Resorption and Osteoclastogenesis by Inhibition of TNF-α Expression in Macrophages

Ren,

Kitaura,

Noguchi

et al. 2024

Calcif Tissue Int

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Renin–angiotensin–aldosterone system plays a crucial role in the regulation of blood pressure and fluid homeostasis. It is reported to be involved in mediating osteoclastogenesis and bone loss in diseases of inflammatory bone resorption such as osteoporosis. Angiotensin-(1–7), a product of Angiotensin I and II (Ang I, II), is cleaved by Angiotensin-converting enzyme 2 and then binds to Mas receptor to counteract inflammatory effects produced by Ang II. However, the mechanism by which Ang-(1–7) reduces bone resorption remains unclear. Therefore, we aim to elucidate the effects of Ang-(1–7) on lipopolysaccharide (LPS)-induced osteoclastogenesis. In vivo, mice were supracalvarial injected with Ang-(1–7) or LPS ± Ang-(1–7) subcutaneously. Bone resorption and osteoclast formation were compared using micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) stain, and real-time PCR. We found that Ang-(1–7) attenuated tumor necrosis factor (TNF)-α, TRAP, and Cathepsin K expression from calvaria and decreased osteoclast number along with bone resorption at the suture mesenchyme. In vitro, RANKL/TNF-α ± Ang-(1–7) was added to cultures of bone marrow-derived macrophages (BMMs) and osteoclast formation was measured via TRAP staining. The effect of Ang-(1–7) on LPS-induced osteoblasts RANKL expression and peritoneal macrophages TNF-α expression was also investigated. The effect of Ang-(1–7) on the MAPK and NF-κB pathway was studied by Western blotting. As a result, Ang-(1–7) reduced LPS-stimulated macrophages TNF-α expression and inhibited the MAPK and NF-κB pathway activation. However, Ang-(1–7) did not affect osteoclastogenesis induced by RANKL/TNF-α nor reduce osteoblasts RANKL expression in vitro. In conclusion, Ang-(1–7) alleviated LPS-induced osteoclastogenesis and bone resorption in vivo via inhibiting TNF-α expression in macrophages.

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Captopril alleviates glucocorticoid-induced osteonecrosis of the femoral head by mediating the ACE2/ Ang-(1-7)/Mas receptor cascade

Cited by 3 publications

References 32 publications

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

Exogenous Angiotensin-(1–7) Provides Protection Against Inflammatory Bone Resorption and Osteoclastogenesis by Inhibition of TNF-α Expression in Macrophages

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