Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice

Abstract

This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and BR signaling pathways in bone.

Tetrahydroxy stilbene glucoside protected against diabetes‐induced osteoporosis in mice with streptozotocin‐induced hyperglycemia

“…SOST, expressed chiefly in bone cells (osteocytes), functionally inactivates β‐catenin signaling pathway, thereby SOST is a physiological inhibitor on bone formation (Zhang, Wang, Song, et al, ). The mRNA expression of SOST was upregulated in bone of diabetic mice, and treatment with TSG statistically suppressed the SOST expression, which well explained the upregulation in β‐catenin expression in bone of diabetic mice upon to TSG treatment.…”

“…The emerging evidences demonstrated the expression of renin–angiotensin system (RAS) components in bone, including renin, renin receptor, angiotensin‐converting enzyme (ACE), ANG II, and its receptors (Zhang et al, ). ANG II, active peptide within RAS, plays a pathological role in development of osteopenia and osteoporosis through activating osteoclastogenesis and inhibiting osteogenesis by binding to Type 1 receptor (AT1R; Nakai et al, ; Shimizu et al, ).…”

“…In vivo and in vitro studies showed that the increased activity of skeletal RAS, especially the overactivation of the renin/renin receptor axis and the ACE/ANG II/AT1R signaling, was detrimental to bone tissue during hyperglycemia (Li et al, ; Yamamoto et al, ; Zhang et al, ; Zhang et al, ). Therefore, the RAS inhibitors, including renin inhibitor, ACE inhibitor (ACEI), and ANG II receptor blocker (ARB), exerted beneficial effects on skeletal system in animal studies (Zhang, Wang, Song, et al, ) and clinical studies (Yamamoto et al, ), even though these drugs in clinic are mainly prescribed for treating hypertension. Whereas, the therapeutic reagents derived from natural products and functional foods are very limited.…”

Monocyte-Specific Knockout of C/ebpα Results in Osteopetrosis Phenotype, Blocks Bone Loss in Ovariectomized Mice, and Reveals an Important Function of C/ebpα in Osteoclast Differentiation and Function

“…C/ebpα f/f LysM-Cre and C/ebpα f/f mice were either dorsal ovariectomized or sham-operated (sham) under anesthetization with a mixture of ketamine:xylazine (80:10 mg/kg) as described (38). Mutant and wild-type mice were compared with Sham or OVX mice (OVX), respectively.…”

“…(7,33) Ovariectomy procedure C/ebpa f/f LysM-Cre and C/ebpa f/f mice were either dorsal ovariectomized (OVX) or sham-operated (sham) under anesthetization with a mixture of ketamine:xylazine (80:10 mg/kg) as described. (37) Mutant and WT mice were compared with sham or OVX mice, respectively. At 4 weeks postoperation, femurs and uteri were harvested for phenotypic and radiological analysis as previously described.…”