Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids

Vidal, N.; Brändström, Helena; Jonsson, Kenneth B.; Ohlsson, Claes

doi:10.1677/joe.0.1590191

Cited by 162 publications

(96 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In vitro data strongly suggest that glucocorticoids enhance the expression of RANKL while downregulating the expression of OPG (8,11,12). In contrast, prednisolone treatment was not associated with a significant increase in the ratio of RANKL to OPG in the bones of wild-type or hRANKL-knockin mice in our in vivo study.…”

Section: Discussionmentioning

confidence: 45%

See 1 more Smart Citation

Prevention of glucocorticoid‐induced bone loss in mice by inhibition of RANKL

Hofbauer¹,

Zeitz²,

Schoppet³

et al. 2009

Arthritis & Rheumatism

116

View full text Add to dashboard Cite

Objective. RANKL has been implicated in the pathogenesis of glucocorticoid-induced osteoporosis. This study was undertaken to evaluate the efficacy of denosumab, a neutralizing monoclonal antibody against human RANKL (hRANKL), in a murine model of glucocorticoid-induced osteoporosis.Methods. Eight-month-old male homozygous hRANKL-knockin mice expressing a chimeric RANKL protein with a humanized exon 5 received 2.1 mg/kg of prednisolone or placebo daily over 4 weeks via subcutaneous slow-release pellets and were additionally treated with phosphate buffered saline or denosumab (10 mg/kg subcutaneously twice weekly). Two groups of wild-type mice were also treated with either prednisolone or vehicle.Results. The 4-week prednisolone treatment induced loss of vertebral and femoral volumetric bone mineral density in the hRANKL-knockin mice. Glucocorticoid-induced bone loss was associated with suppressed vertebral bone formation and increased bone resorption, as evidenced by increases in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, TRAP-5b protein in bone extracts, serum levels of TRAP-5b, and urinary excretion of deoxypyridinoline. Denosumab prevented prednisoloneinduced bone loss by a pronounced antiresorptive effect. Biomechanical compression tests of lumbar vertebrae revealed a detrimental effect of prednisolone on bone strength that was prevented by denosumab.Conclusion. Our findings indicate that RANKL inhibition by denosumab prevents glucocorticoidinduced loss of bone mass and strength in hRANKLknockin mice.

show abstract

Section: Discussionmentioning

confidence: 45%

“…Furthermore, glucocorticoids enhance the expression of RANKL (8,11) and inhibit the expression of osteoprotegerin (OPG) (8,11,12). RANKL has been identified as an essential cytokine for osteoclast differentiation and activation (13), and OPG represents its naturally occurring inhibitor (14).…”

mentioning

confidence: 99%

Prevention of glucocorticoid‐induced bone loss in mice by inhibition of RANKL

Hofbauer¹,

Zeitz²,

Schoppet³

et al. 2009

Arthritis & Rheumatism

116

View full text Add to dashboard Cite

show abstract

“…In particular, hormones such as PTH [10] and glucocorticoids [11,12] have been reported to decrease OPG concentrations while anabolic agents such as estrogens, transforming growth factor β, related bone morphogenic factor and thrombopoietin [13][14][15][16] have been shown to enhance the OPG production in the osteoblastic and bone stromal cells. Recent studies [17][18][19] have described a bimodal pattern for the variation along the 24-h scale of circulating PTH, with a major peak during the night and a secondary peak in the late afternoon.…”

Section: Discussionmentioning

confidence: 99%

Circasemidian rather than circadian variation of circulating osteoprotegerin in clinical health

Tarquini

Mazzoccoli

Dolenti

et al. 2005

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Osteoprotegerin (OPG) serves as a soluble decoy receptor for RANKL to inhibit osteoclast formation and activity. Hormones such as PTH and glucocorticoids have been reported to decrease OPG concentrations, while estrogens, transforming growth factor b, related bone morphogenic factor and thrombopoietin reportedly enhance the OPG production in the osteoblastic and bone stromal cells. Since bone turnover shows a prominent circadian rhythm in laboratory animals and humans, with bone resorption increasing at night, we investigated the time structure of circulating OPG concentrations in a group of nine healthy subjects (six women and three men; in the age range of 26-49 years). Blood samples for OPG determination were collected every 4 h for 24 h on the same day, starting at 08:00 in the morning. Data were analyzed by inferential statistical procedures, including the single and population-mean cosinor. A 12-h component was found to characterize serum OPG concentrations (P = 0.038) with peak concentrations around noon and midnight. No statistically significant circadian rhythm of OPG concentrations could be found by cosinor in our study population. The mean 24-h OPG concentration was higher in women than in men (mean ± S.E.: 3.13 ± 0.44 vs. 1.94 ± 0.26 pmol/1, Student t = 2.325, P = 0.053). Since PTH concentrations also exhibit a bimodal pattern along the 24-h scale, PTH may be tested as a putative determinant of the observed changes in serum concentrations of osteoprotegerin.

show abstract

“…35 This suggests a clinically relevant relationship between immunosuppressive therapy and OPG, which has been postulated from in vitro studies in which both glucocorticoids and CsA were shown to markedly downregulate OPG production in human osteoblastic cell lines. [36][37][38] Reduced BMD and partially increased serum levels of the beta-crosslaps, both reflecting increased bone resorption, apparently are in contrast to elevated OPG. The detection system for OPG measures total OPG, that is, it cannot discriminate between free OPG and OPG as a complex with RANKL (RANK ligand).…”

Section: Discussionmentioning

confidence: 99%

Bone metabolism in patients more than five years after bone marrow transplantation

Kerschan‐Schindl

Mitterbauer

Füreder

et al. 2004

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG) -an antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P ¼ 0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.

show abstract

Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids

Cited by 162 publications

References 29 publications

Prevention of glucocorticoid‐induced bone loss in mice by inhibition of RANKL

Prevention of glucocorticoid‐induced bone loss in mice by inhibition of RANKL

Circasemidian rather than circadian variation of circulating osteoprotegerin in clinical health

Bone metabolism in patients more than five years after bone marrow transplantation

Contact Info

Product

Resources

About