Increased bone loss and amount of osteoclasts in kinin B1 receptor knockout mice

Gonçalves-Zillo, Thais Oliveira; Pugliese, Lívia Souza; Sales, Vicência; Mori, Marcelo A.; Squaiella-Baptistão, Carla Cristina; Longo-Maugéri, Ieda Maria; Lopes, José Daniel; Oliveira, Sérgio Ferreira de; Monteiro, Ana Carolina; Pesquero, João Bosco

doi:10.1111/jcpe.12097

Cited by 18 publications

(11 citation statements)

References 37 publications

(37 reference statements)

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“…However, WT C57/BL6 STZ-diabetic mice showed a marked reduction of collagen contents, with increased osteoblast apoptosis, with delayed healing regeneration, likely related to the up-regulation of B 1 R. detect any significant difference among the immunolabeling of RANK, RANKL, and OPG in non-diabetic and diabetic WT C57/ BL6 or B 1 RKO mice. GonS calves-Zillo et al, (2013) demonstrated an increased number of osteoclasts in animals lacking B 1 R by inducing in vitro differentiation of bone marrow cells with M-CSF and RANKL, contrasting to some degree with our data. In contrast, a recent study demonstrated that activation of B 1 R or B 2 R reduces osteoblast differentiation and stimulates osteoclasts, by mechanisms involving NF-kB-dependent gene regulation in vitro (Srivastava et al, 2014), reinforcing our results.…”

Section: Discussioncontrasting

confidence: 99%

“…This difference might be explained by: (i) the chemically‐induced model of type 1 diabetes adopted by us; (ii) the use of B 1 RKO mice instead of double B 1 R/B 2 R KO animals; and (iii) the evaluation methods for active bone remodeling, following the creation of a bone defect. It was shown that B 1 RKO mice displayed increased bone resorption in a model of ligature‐induced periodontitis; however, the authors did not assess the specific influence of diabetes, and there was an infectious component in their experimental approach (Gonçalves‐Zillo et al, ), which is not the case in this study.…”

Section: Discussionmentioning

confidence: 69%

“…In contrast, a study conducted by Kakoki et al (2010) demonstrated that double B 1 R/B 2 R gene deletion resulted in enhanced kidney injury, neuropathy, and bone mineral density loss, when evaluated in Akita diabetic mice. A protective role for kinin receptors has also been suggested more recently (GonS calves-Zillo et al, 2013) by demonstrating that B 1 R knockout (B 1 RKO) mice show an increase in bone resorption following ligature-induced periodontal disease, although the influence of diabetes has not been examined by the authors.…”

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confidence: 99%

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Kinin B₁ Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

Cignachi

Pesquero

Oliveira

et al. 2015

Journal Cellular Physiology

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The effects of kinin B1 receptor (B1 R) deletion were examined on femur bone regeneration in streptozotocin (STZ)-type 1 diabetes. Diabetes induction in wild-type C57/BL6 (WTC57BL6) mice led to decrease in body weight and hyperglycemia, compared to the non-diabetic group of the same strain. The lack of B1 R did not affect STZ-elicited body weight loss, but partially prevented hyperglycemia. Diabetic mice had a clear delay in bone regeneration, and displayed large areas of loose connective tissue within the defects, with a reduced expression of the mineralization-related protein osteonectin, when compared to the non-diabetic WTC57/BL6. The non-diabetic and diabetic B1 R knockout (B1 RKO) mice had bone regeneration levels and osteonectin expression comparable to that seen in control WTC57/BL6 mice. WTC57/BL6 STZ-diabetic mice also showed a marked reduction of collagen contents, with increased immunolabeling for the apoptosis marker caspase-3, whereas diabetic B1 RKO had collagen levels and caspase-3 activity comparable to those observed in non-diabetic WTC57/BL6 or B1 RKO mice. No significant difference was detected in the number of tartrate-resistant acid phosphatase (TRAP)-stained cells, or in RANK/RANKL/OPG system immunolabeling throughout the experimental groups. Data bring novel evidence on the relevance of kinin B1 R under type 1 diabetes with regards to its role in bone regeneration.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 99%

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Kinin B₁ Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

Cignachi

Pesquero

Oliveira

et al. 2015

Journal Cellular Physiology

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“…). Bradykinin is known as an inflammatory mediator and is also involved in bone metabolism . Thus, our results suggest that inflammatory signals in bone tissue are first received by osteoblasts, and are then transferred to sensory nerves.…”

Section: Discussionmentioning

confidence: 63%

Bidirectional communication between sensory neurons and osteoblasts in an in vitro coculture system

et al. 2017

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Recent studies have revealed that the sensory nervous system is involved in bone metabolism. However, the mechanism of communication between neurons and osteoblasts is yet to be elucidated. In this study, we investigated the signaling pathways between sensory neurons of the dorsal root ganglion (DRG) and the osteoblast-like MC3T3-E1 cells using an in vitro coculture system. Our findings indicate that signal transduction from DRG-derived neurons to MC3T3-E1 cells is suppressed by antagonists of the AMPA receptor and the NK receptor. Conversely, signal transduction from MC3T3-E1 cells to DRG-derived neurons is suppressed by a P2X receptor antagonist. Our results suggest that these cells communicate with each other by exocytosis of glutamate, substance P in the efferent signal, and ATP in the afferent signal.

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“…Bradykinin normally exerts its effects through the activation of two seven transmembrane G protein-coupled receptors, named B1 and B2. It was reported that bradykinin can decrease the differentiation of osteoblasts with concomitant increase in osteoclast formation, consequently stimulating bone resorption and reduce BMD, [34][35][36] and that the lack of both B1R and B2R accelerated the loss of bone minerals.…”

Section: 4)mentioning

confidence: 99%

Involvement of Renin–Angiotensin System in Damage of Angiotensin-Converting Enzyme Inhibitor Captopril on Bone of Normal Mice

Liu

Wang

Zhang

2015

Biological & Pharmaceutical Bulletin

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This study was performed to investigate the effect of angiotensin-converting enzyme inhibitor, captopril, on bone metabolism and histology, and the action of captopril on the components of the skeletal reninangiotensin system (RAS) and bradykinin receptor in normal male mice. The mice were orally administered captopril (10 mg/kg) for 4 weeks with vehicle-treated mice as normal control. The histology of trabecular bone at the distal femoral end was determined by hematoxylin & eosin, Safranin O and Masson-Trichrome staining. The captopril-treated mice showed a decreased level of testosterone ( p<0.05) and procollagen type I N-terminal propeptide (p<0.05) in serum as compared to those in the control group. Captopril has detrimental effects on trabecular bone as demonstrated by the loss of cancellous bone mass and network connections as well as changes to the chondrocytes zone. The expression of angiotensin-converting enzyme (p<0.05), renin receptor (p<0.01), angiotensin II (p<0.05) and bradykinin receptor 2 (p<0.05) was significantly up-regulated following the captopril treatment. Thus, the potential underlying mechanism of the damage of captopril on bone can be attributed the increased activity of local bone RAS and the activation of bradykinin receptor.Key words renin-angiotensin system; bradykinin receptor; captopril; bone The renin-angiotensin system (RAS) is a hormonal cascade that is thought to act as a master controller of blood pressure and fluid balance within the body.1) In addition to the systemic RAS, there is a fully functional RAS in local tissue, which is postulated to participate in various physiological and pathological processes such as insulin secretion, 2) glomerular sclerosis, 3) renal inflammation, 4) atherosclerosis, 5) and cardiac hypertrophy. 6) Recent in vivo studies showed that the components of RAS, such as renin, angiotensin-converting enzyme (ACE), and angiotensin II (Ang II) receptors, were expressed in the local milieu of bone, [7][8][9][10] and in vitro study identified the expression of Ang II receptors in primary osteoblasts derived from newborn mouse calvaria, 7) indicating the components of RAS are expressed locally in bone microenvironment. Our further animal studies demonstrated that the local RAS in bone was involved in age-related osteoporosis of aging mice, 11) and bone deteriorations of mice with either obstructive nephropathy 12) or type 1 diabetes.13) Other groups elucidated the involvement of skeletal RAS in the process of fracture healing in a mouse femur fracture model, 14) and the steroid-induced osteonecrosis in rabbits 10) as well as the development of postmenopausal osteoporosis in ovariectomized (OVX) animal models 15,16) and glucocorticoid-induced osteoporosis. 9) Therefore, it concludes that the local RAS exists in bone tissue and plays an important role in local bone metabolism.The main effector peptide Ang II in RAS is formed from angiotensin I by the action of ACE, a key molecule in this system. Patients treated with an ACE inhibitor (ACEI) showed an increas...

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Increased bone loss and amount of osteoclasts in kinin B1 receptor knockout mice

Abstract: Bdkrb1 participates in the pathogenesis of LIEP bone loss possibly through mechanisms that involve modulation of the TH 17 response, thereby demonstrating its role in the development of periodontitis.

Cited by 18 publications

References 37 publications

Kinin B₁ Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

Kinin B₁ Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

Bidirectional communication between sensory neurons and osteoblasts in an in vitro coculture system

Involvement of Renin–Angiotensin System in Damage of Angiotensin-Converting Enzyme Inhibitor Captopril on Bone of Normal Mice

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Increased bone loss and amount of osteoclasts in kinin B1 receptor knockout mice

Abstract: Bdkrb1 participates in the pathogenesis of LIEP bone loss possibly through mechanisms that involve modulation of the TH 17 response, thereby demonstrating its role in the development of periodontitis.

Cited by 18 publications

References 37 publications

Kinin B1 Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

Kinin B1 Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

Bidirectional communication between sensory neurons and osteoblasts in an in vitro coculture system

Involvement of Renin–Angiotensin System in Damage of Angiotensin-Converting Enzyme Inhibitor Captopril on Bone of Normal Mice

Contact Info

Product

Resources

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Kinin B₁ Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice

Kinin B₁ Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice