Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands

Horowitz, Mark C.; Xi, Yougen; Wilson, Kimberly; Kacena, Melissa A.

doi:10.1016/s1359-6101(00)00030-7

Cited by 196 publications

(189 citation statements)

References 67 publications

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“…This could be due to intrinsic limitations of currently available ELISAs, which utilize OPG as an immobilized capture component and therefore may be interfered with by OPG content in the sample (Kinpara et al 2000). RANKL/OPG ratio is admittedly a major determinant of osteoclastogenesis, osteoclast activity and apoptosis, and therefore of bone resorption (Hofbauer & Heufelder 2000, Horowitz et al 2001. We have confirmed a strong inhibitory effect of both cortisol (at physiological and supraphysiological concentrations) and Dex on OPG release.…”

Section: Figuresupporting

confidence: 54%

Autocrine down-regulation of glucocorticoid receptors by interleukin-11 in human osteoblast-like cell lines

Dovio¹,

Sartori²,

Rg³

et al. 2003

Journal of Endocrinology

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It has recently been suggested that interleukin (IL)-11 plays a role in the pathogenesis of glucocorticoid (GC)-induced osteoporosis. IL-11 belongs to the gp130 cytokine family, which includes also IL-6. We have previously investigated GC-IL-6 interplay, showing that GC inhibits IL-6 release and IL-6 up-regulates GC receptor (GR) numbers in the human osteoblast-like cell lines Saos-2 and MG-63, which constitutively have an opposite pattern of expression for GR, IL-11, IL-6, alkaline phosphatase and osteoprotegerin (OPG). The aim of this study was to investigate GC-IL-11 interplay in the same two cell lines. First, cells were incubated with cortisol (0·01-1 µM) for 20 h in the presence and in the absence of a known IL-11 secretagogue (IL-1 ); cell media were assayed for IL-11 by ELISA. Secondly, cells were incubated with IL-11 (0·1-100 ng/ml) or specific anti-IL-11 monoclonal antibody for 20 h, and then assayed for GR by a radioligand binding assay. Similar to IL-6, both constitutive and IL-1 -inducible IL-11 release were dose-dependently inhibited by cortisol (P<0·01); at variance with IL-6, exogenous IL-11 dose-dependently decreased GR numbers in MG-63 cells (P<0·05), while anti-IL-11 antibody significantly increased GR numbers in both cell lines (P<0·05). IL-11-induced reduction of GR in MG-63 cells was confirmed by Western blot analysis. While exerting opposite effects on GR numbers, neither IL-6 nor IL-11 significantly modified GC-dependent inhibition of OPG release. Our data indicate that even physiological concentrations of cortisol negatively modulate IL-11 secretion and demonstrate, for the first time, an inhibitory effect of the cytokine on GR. Thus, the concept of autocrine-paracrine loops that modulate GC action and involve gp130 cytokines is corroborated. These loops could have clinical relevance for the dynamics of bone loss in patients given GC and having high concentrations of these cytokines in the bone microenvironment.

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Section: Figuresupporting

confidence: 54%

Autocrine down-regulation of glucocorticoid receptors by interleukin-11 in human osteoblast-like cell lines

Dovio¹,

Sartori²,

Rg³

et al. 2003

Journal of Endocrinology

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“…Although it is widely accepted that RANKL plays a central role in osteoclastogenesis, (31)(32)(33) there are few reports focusing on RANKL in the context of subcellular protein trafficking in osteoblastic cells. Previously we have shown that the subcellular trafficking of RANKL in osteoblastic cells is strictly regulated via a series of complicated processes.…”

Section: Discussionmentioning

confidence: 99%

Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis

Aoki

Honma

Kariya

et al. 2010

Journal of Bone and Mineral Research

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The amount of the receptor activator of NF-kB ligand (RANKL) on the osteoblastic cell surface is considered to determine the magnitude of the signal input to osteoclast precursors and the degree of osteoclastogenesis. Previously, we have shown that RANKL is localized predominantly in lysosomal organelles, but little is found on the osteoblastic cell surface, and consequently, the regulated subcellular trafficking of RANKL in osteoblastic cells is important for controlled osteoclastogenesis. Here we have examined the involvement of osteoprotegerin (OPG), which is currently recognized as a decoy receptor for RANKL, in the regulation of RANKL behavior. It was suggested that OPG already makes a complex with RANKL in the Golgi apparatus and that the complex formation is necessary for RANKL sorting to the secretory lysosomes. It was also shown that each structural domain of OPG is indispensable for exerting OPG function as a traffic regulator. In particular, the latter domains of OPG, whose physiologic functions have been unclear, were indicated to sort RANKL molecules to lysosomes from the Golgi apparatus. In addition, the overexpression of RANK-OPG chimeric protein, which retained OPG function as a decoy receptor but lost the function as a traffic regulator, inhibited endogenous OPG function as a traffic regulator selectively in osteoblastic cells and resulted in the upregulation of osteoclastogenic ability despite the increased number of decoy receptor molecules. Conclusively, OPG function as a traffic regulator for RANKL is crucial for regulating osteoclastogenesis at least as well as that as a decoy receptor. ß

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“…Estrogen suppresses RANK ligand (RANKL) production and increases osteoprotegerin production [15]. Loss of estrogen allows for more RANKL to reach its receptor RANK on the osteoclast, resulting in increased osteoclastic activity and lifespan [42,96].…”

Section: Diagnosis and Treatment Of Diseases Associated With Impairedmentioning

confidence: 99%

Short-term and Long-term Orthopaedic Issues in Patients With Fragility Fractures

Bukata

Kates

O’Keefe

2011

Clinical Orthopaedics &Amp; Related Research

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Background Patients with impaired bone quality who suffer a fragility fracture face substantial challenges in both their short-and long-term care. In addition to poor bone quality, many of these patients have multiple medical comorbidities that alter their surgical risk and affect their ultimate functional recovery. Some medical issues can contribute to the altered bone quality and must be addressed to prevent future fractures. Questions/purposes This review summarizes the modifications in perioperative management and fracture fixation in patients with common fragility fractures who have impaired bone quality. It also summarizes the postoperative diagnosis and treatment of secondary causes of impaired bone quality in these patients. Methods We performed a PubMed search, and literature published after 2000 was prioritized, with the exception of benchmark clinical trial studies published before 2000. Results Patients with altered bone quality require rapid perioperative management of multiple medical comorbidities. Implant selection in patients with poor quality bone should permit early weightbearing, and constructs should maximize surface area contact with the remaining bone. Long-term diagnosis and treatment of other disease states contributing to poor bone quality (vitamin D deficiency/ insufficiency, hypothyroidism, hyperthyroidism, hyperparathyroidism, Cushing's disease, and hypogonadism) must occur to minimize the chances of future fractures. Conclusions Recognition of patients with impaired bone quality and proper treatment of their special needs in both the short and long term are essential for their best opportunity for maximal functional recovery and prevention of future fractures.

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Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands

Cited by 196 publications

References 67 publications

Autocrine down-regulation of glucocorticoid receptors by interleukin-11 in human osteoblast-like cell lines

Autocrine down-regulation of glucocorticoid receptors by interleukin-11 in human osteoblast-like cell lines

Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis

Short-term and Long-term Orthopaedic Issues in Patients With Fragility Fractures

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