Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

Wasilewska, Anna; Rybi-Szumińska, Agnieszka; Zoch-Zwierz, W

doi:10.1007/s00467-010-1583-1

Cited by 32 publications

(28 citation statements)

References 43 publications

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“…We observed an approximate 2-fold increase in the RANKL/OPG ratio using serum specimens from CHIKV patients. This is similar in magnitude to the increases in RANKL/OPG ratios reported for patients with postmenopausal osteoporosis (1.8-fold) (58), osteoarthritis patients (ϳ1.5-fold) (59), and children with osteoporosis due to glucocorticoid therapy for idiopathic nephrotic syndrome (ϳ1.5-fold) (60).…”

Section: Discussionsupporting

confidence: 83%

Bindarit, an Inhibitor of Monocyte Chemotactic Protein Synthesis, Protects against Bone Loss Induced by Chikungunya Virus Infection

Chen

Foo

Taylor

et al. 2015

J Virol

108

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The recent global resurgence of arthritogenic alphaviruses, in particular chikungunya virus (CHIKV), highlights an urgent need for the development of therapeutic intervention strategies. While there has been significant progress in defining the pathophysiology of alphaviral disease, relatively little is known about the mechanisms involved in CHIKV-induced arthritis or potential therapeutic options to treat the severe arthritic symptoms associated with infection. Here, we used microcomputed tomographic (CT) and histomorphometric analyses to provide previously undescribed evidence of reduced bone volume in the proximal tibial epiphysis of CHIKV-infected mice compared to the results for mock controls. This was associated with a significant increase in the receptor activator of nuclear factor-B ligand/osteoprotegerin (RANKL/OPG) ratio in infected murine joints and in the serum of CHIKV patients. The expression levels of the monocyte chemoattractant proteins (MCPs), including MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7, were also highly elevated in joints of CHIKV-infected mice, accompanied by increased cellularity within the bone marrow in tibial epiphysis and ankle joints. Both this effect and CHIKV-induced bone loss were significantly reduced by treatment with the MCP inhibitor bindarit. Collectively, these findings demonstrate a unique role for MCPs in promoting CHIKV-induced osteoclastogenesis and bone loss during disease and suggest that inhibition of MCPs with bindarit may be an effective therapy for patients affected with alphavirus-induced bone loss. IMPORTANCE Arthritogenic alphaviruses, including chikungunya virus (CHIKV) and Ross River virus (RRV), cause worldwide outbreaks of polyarthritis, which can persist in patients for months following infection. Previous studies have shown that host proinflammatory soluble factors are associated with CHIKV disease severity. Furthermore, it is established that chemokine (C-C motif) ligand 2 (CCL2/MCP-1) is important in cellular recruitment and inducing bone-resorbing osteoclast (OC) formation. Here, we show that CHIKV replicates in bone and triggers bone loss by increasing the RANKL/OPG ratio. CHIKV infection results in MCP-induced cellular infiltration in the inflamed joints, and bone loss can be ameliorated by treatment with an MCP-inhibiting drug, bindarit. Taken together, our data reveal a previously undescribed role for MCPs in CHIKV-induced bone loss: one of recruiting monocytes/OC precursors to joint sites and thereby favoring a pro-osteoclastic microenvironment. This suggests that bindarit may be an effective treatment for alphavirus-induced bone loss and arthritis in humans.

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Section: Discussionsupporting

confidence: 83%

Bindarit, an Inhibitor of Monocyte Chemotactic Protein Synthesis, Protects against Bone Loss Induced by Chikungunya Virus Infection

Chen

Foo

Taylor

et al. 2015

J Virol

108

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“…Clinical research also showed that OPG levels are significantly higher in patients with chronic kidney disease (CKD) compared with age- and sex-matched controls, and increasing OPG levels have a linear relationship with adverse renal function [36–39]. Elevated OPG is associated with all-cause mortality in CKD stage 4 and 5 patients in addition to vascular calcification [40].…”

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin Inhibits Calcification of Vascular Smooth Muscle Cell via Down Regulation of the Notch1-RBP-Jκ/Msx2 Signaling Pathway

et al. 2013

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ObjectiveVascular calcification is a common pathobiological process which occurs among the elder population and in patients with diabetes and chronic kidney disease. Osteoprotegerin, a secreted glycoprotein that regulates bone mass, has recently emerged as an important regulator of the development of vascular calcification. However, the mechanism is not fully understood. The purpose of this study is to explore novel signaling mechanisms of osteoprotegerin in the osteoblastic differentiation in rat aortic vascular smooth muscle cells (VSMCs).Methods and ResultsVSMCs were isolated from thoracic aorta of Sprague Dawley rats. Osteoblastic differentiation of VSMCs was induced by an osteogenic medium. We confirmed by Von Kossa staining and direct cellular calcium measurement that mineralization was significantly increased in VSMCs cultured in osteogenic medium; consistent with an enhanced alkaline phosphatase activity. This osteoblastic differentiation in VSMCs was significantly reduced by the addition of osteoprotegerin in a dose responsive manner. Moreover, we identified, by real-time qPCR and western blotting, that expression of Notch1 and RBP-Jκ were significantly up-regulated in VSMCs cultured in osteogenic medium at both the mRNA and protein levels, these effects were dose-dependently abolished by the treatment of osteoprotegerin. Furthermore, we identified that Msx2, a downstream target of the Notch1/RBP-Jκ signaling, was markedly down-regulated by the treatment of osteoprotegerin.ConclusionOsteoprotegerin inhibits vascular calcification through the down regulation of the Notch1-RBP-Jκ signaling pathway.

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“…3). An increasing RANKL/OPG ratio after fracture is considered to tilt the balance of RANKL and OPG toward bone resorptive status (17), since this balance is critically important for bone remodeling and the preservation of bone mass (23). The RANKL-OPG balance may affect osteoclast activity, which is why it has been suggested that the serum RANKL/OPG ratio is a critical factor for determining osteoclast activation (24).…”

Section: Discussionmentioning

confidence: 99%

The role of the serum RANKL/OPG ratio in the healing of intertrochanteric fractures in elderly patients

Wang

Zhang

et al. 2013

Molecular Medicine Reports

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Intertrochanteric fractures occur most commonly in elderly patients. Osteoblasts and osteoclasts have been reported to be regulated by the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), during bone modeling and remodeling, respectively. Based on these observations, we hypothesized that the serum levels of RANKL, OPG and the RANKL/OPG ratio are important in the healing of intertrochanteric fractures in elderly patients. Enzyme-linked immunosorbent assays were used to measure the serum concentrations of RANKL and OPG in 36 elderly patients with intertrochanteric fractures and 30 age-matched healthy control subjects, at baseline and 4, 8 and 12 weeks following injury. The RANKL/OPG ratio in the two groups was also evaluated. Similar trends in RANKL and OPG levels were detected during the fracture healing process. The serum levels of RANKL and OPG were higher in the fracture group than in the controls, and were significantly higher at baseline and 4 weeks following injury (P<0.05). Notably, although the RANKL/OPG ratio gradually increased during healing, it was lower in the fracture group than in the control group. The RANKL/OPG ratio was significantly lower immediately after and 4 weeks after injury in the fracture group (P<0.05). Our data suggest a close correlation between higher serum levels of RANKL and OPG and the fracture healing process, indicating that RANKL and OPG are involved in fracture healing. The serum RANKL/OPG ratio also appears to be significant in the healing of intertrochanteric fractures in elderly patients.

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Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

Cited by 32 publications

References 43 publications

Bindarit, an Inhibitor of Monocyte Chemotactic Protein Synthesis, Protects against Bone Loss Induced by Chikungunya Virus Infection

Bindarit, an Inhibitor of Monocyte Chemotactic Protein Synthesis, Protects against Bone Loss Induced by Chikungunya Virus Infection

Osteoprotegerin Inhibits Calcification of Vascular Smooth Muscle Cell via Down Regulation of the Notch1-RBP-Jκ/Msx2 Signaling Pathway

The role of the serum RANKL/OPG ratio in the healing of intertrochanteric fractures in elderly patients

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