Acute Effects of Glucocorticoids on Serum Markers of Osteoclasts, Osteoblasts, and Osteocytes

Marešová, Kristýna Brábníková; Pavelka, Karel; Stepan, Jan J.

doi:10.1007/s00223-012-9684-4

Cited by 69 publications

(53 citation statements)

References 50 publications

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“…These data indicate that osteoclast absorption was greater than osteoblast formation. Recently, it was reported that overexpression of DKK-1 during inflammation not only resulted in inhibition of bone formation but also stimulated the activity of osteoclasts [34][35][36]. In our study, excess DKK-1 was found in the ankle and femur of CIA rats at 8 weeks after immunization.…”

Section: Discussionsupporting

confidence: 57%

“…In our study, in the process of osteoporosis caused by CIA, upregulation of DKK-1 not only reduced systemic bone mass, as a result of activation of osteoclasts, resulting in enhanced bone resorption [35,36], but also affected bone growth by inhibiting the differentiation of osteoblasts [30] as well as the transport of substances osteoblasts need. Furthermore, our findings suggest that activation of the Wnt signaling pathway by inhibition of DKK-1 is a target for prevention and treatment of osteoporosis induced by RA.…”

Section: Discussionmentioning

confidence: 86%

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Secondary osteoporosis in collagen-induced arthritis rats

Xiong

Zhang

et al. 2015

J Bone Miner Metab

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Numerous studies have demonstrated that rheumatoid arthritis (RA) is often associated with bone loss; however, few experiments have focused on cancellous and cortical bone changes in rats during the process of arthritis. We have investigated bone changes in rats with collagen-induced arthritis (CIA) and have explored the characteristics of how RA induces osteoporosis by means of bone histomorphometry, bone biomechanics studies, bone mineral density studies, micro computer tomography, enzyme-linked immunosorbant assay, immunohistochemistry, and Western blot analysis. Bone mineral density of the femur and lumbar vertebrae and biomechanical properties of the femur were decreased in CIA rats. Trabecular bone volume of the tibia and lumbar vertebrae was decreased whereas bone resorption was increased in CIA rats. Bone formation of the tibial shaft in periosteal surfaces was decreased in CIA rats. Furthermore, the trabecular bone loss in CIA rats was severer at 16 weeks than at 8 weeks, as was cortical bone loss. The serum level of tumor necrosis factor α in CIA rats was increased, and the expression of dickkopf 1 and that of receptor activator of nuclear factor κB (RANKL) ligand (RANKL) in the ankle joints were also increased, but the expression of osteoprotegerin (OPG) was decreased. We conclude that CIA rats developed systemic osteoporosis, and that osteoporosis became more serious with CIA development. The mechanism may be related to the increase of bone resorption in cancellous bone cause by upregulation of the expression of DKK-1 and regulation of the RANKL/RANK/OPG signaling pathway, and the decrease of bone formation in cortical bone caused by an increase in the expression of DKK-1.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 86%

Secondary osteoporosis in collagen-induced arthritis rats

Xiong

Zhang

et al. 2015

J Bone Miner Metab

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“…Thirdly , it is likely that the marked change in the drug treatment and in particular the use of glucocorticoids could contribute to the rapid decrease of sclerostin after transplantation. In a study with 17 patients suffering from various medical pathologies requiring systemic steroid therapy, acute treatment with glucocorticoids was found to decrease sclerostin levels, an effect that is probably linked to glucocorticoid-induced apoptosis of osteocytes [19]. Contrary, Gifre et al showed an increase in sclerostin values in patients treated one year with glucocorticoids [20].…”

Section: Discussionmentioning

confidence: 99%

Sclerostin Blood Levels Before and After Kidney Transplantation

Bonani

Rodríguez

Fehr

et al. 2014

Kidney Blood Press Res

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Background/Aims: Sclerostin is secreted by osteocytes. As a circulating inhibitor of the Wnt-signaling pathway it inhibits bone formation and contributes to the development of osteoporosis. Sclerostin levels are elevated in patients with chronic kidney disease and end-stage renal disease. Since data for patients after kidney transplantation are scarce, we have prospectively measured sclerostin levels before and during the first year after renal transplantation and have examined the association of sclerostin with parameters of bone mineral metabolism and with bone mineral density. Methods: Sclerostin levels were measured by ELISA in 42 consecutive renal transplant recipients before and at defined intervals in the first year after transplantation. Bone mineral density was measured by dual energy X-ray absorptiometry. Results: Pre-transplant serum sclerostin levels were elevated in all patients (61.8 ± 32.3 pmol/l, normal range 20-30 pmol/l). Within 15 days after transplantation and correlating with the improvement of renal function, sclerostin levels dropped to 21.0 ± 14.7 pmol/l and subsequently increased to 23.8 ± 14.9 and 28.0 ± 16.8 pmol/l after 6 and 12 months, respectively (P<0.001). A linear mixed model indicated that pre-transplant sclerostin levels (P<0.001) and time after transplantation (P<0.001) were the most important predictors for the rise of post-transplant sclerostin levels. No correlation was found between post-transplant sclerostin levels and bone mineral density. Conclusions: The rapid reduction of elevated serum sclerostin levels shortly after kidney transplantation parallels the improvement of renal function, but contrasts with the more delayed improvement of hyperparathyroidism. The normalization of both hormones could contribute to improved bone health after renal transplantation.

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“…after short-and long-time treatment with glucocorticoids in mice and rats [Yao et al, 2008;Ren et al, 2015a], but also in male humans after 96-hour treatment with dexamethasone [Brabnikova Maresova et al, 2013]. They discussed apoptotic effects of dexamethasone on osteocytes as a possible reason.…”

Section: Discussionmentioning

confidence: 99%

Rat Osteosarcoma Cells as a Therapeutic Target Model for Osteoregeneration via Sclerostin Knockdown

Sedaghati

Jahroomishirazi²,

Starke

et al. 2016

Cells Tissues Organs

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There are various conceptually different strategies to improve bone regeneration and to treat osteoporosis, each with distinct inherent advantages and disadvantages. The use of RNA interference strategies to suppress the biological action of catabolic factors or antagonists of osteogenic proteins is promising, and such strategies can be applied locally. They are comparably inexpensive and do not suffer from stability problems as protein-based approaches. In this study, we focus on sclerostin, encoded by the SOST gene, a key regulator of bone formation and remodeling. Sclerostin is expressed by mature osteocytes but also by late osteogenically differentiated cells. Thus, it is difficult and requires long-term cultures to investigate the effects of SOST silencing on the expression of osteogenic markers using primary cells. We, therefore, selected a rat osteosarcoma cell line, UMR-106, that has been shown to express SOST and secrete sclerostin in a comparable fashion as late osteoblasts and osteocytes. We investigated the effects of differentiating supplements on SOST expression and sclerostin secretion in UMR-106 cells and found that addition of 100 ng/ml of bone morphogenetic protein (BMP)-2 strongly induced sclerostin secretion, whereas dexamethasone inhibited secretion. Effects of silencing SOST in UMR-106 cells cultured in various differentiation media including BMP-2 and/or dexamethasone were determined next with the aim to find promising test conditions for a readout system for the evaluation of future small interfering RNA release formulations for local induction of bone formation. We found a direct correlation between attenuated SOST expression and an increase in the osteogenic potential of UMR-106 cells. The combination of SOST silencing and BMP-2 could synergistically improve osteogenic factors. A lowered proliferation rate in silenced groups may indicate a faster switch to differentiation.

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Acute Effects of Glucocorticoids on Serum Markers of Osteoclasts, Osteoblasts, and Osteocytes

Cited by 69 publications

References 50 publications

Secondary osteoporosis in collagen-induced arthritis rats

Secondary osteoporosis in collagen-induced arthritis rats

Sclerostin Blood Levels Before and After Kidney Transplantation

Rat Osteosarcoma Cells as a Therapeutic Target Model for Osteoregeneration via Sclerostin Knockdown

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