Neutralization of Interleukin-11 Activity Decreases Osteoclast Formation and Increases Cancellous Bone Volume in Ovariectomized Mice

Shaughnessy, Stephen G.; Walton, Kimberly J.; Deschamps, Paula; Butcher, Martin; Beaudin, Suzanne

doi:10.1006/cyto.2002.1981

Cited by 20 publications

(10 citation statements)

References 40 publications

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“…Because of the low bone turnover resulting from IL‐11Rα ablation, a phenotype closely related to that observed in the ERα −/− mouse, (34) and the hypothesis that IL‐11 may mediate the effects of estradiol on bone, (12–14) we set out to determine whether IL‐11Rα is required for the effects of estradiol on bone or in estrogen deficiency bone loss. Ovariectomy and replacement estradiol treatment were carried out in adult wildtype and IL ‐ 11Rα1 −/− mice.…”

Section: Resultsmentioning

confidence: 78%

“…ER α −/− mice, which have a similar trabecular bone phenotype to the IL ‐ 11Rα1 −/− , also showed dramatically elevated circulating testosterone and estradiol levels and were not responsive to estradiol treatment (34) . It has been suggested that effects of estrogen and estrogen deficiency may be mediated by changes in IL‐6 and/or IL‐11 (11–14) . Previous work in the IL ‐ 6 −/− mouse did not show bone loss or increased bone turnover after ovariectomy, indicating that IL‐6 may play an important role in the loss of bone associated with estrogen deficiency (20) .…”

Section: Discussionmentioning

confidence: 99%

“…Whereas IL‐6, but not IL‐11, seems to regulate both estradiol and progesterone levels in human granulosa cells, (9,10) the circulating levels of both cytokines seem to depend on estrogen status in human subjects (11) . This, coupled with the stimulatory effects of IL‐6 and IL‐11 on osteoblast and osteoclast differentiation, (2–7) has led to the hypothesis that the effects of estrogen and estrogen deficiency may be mediated by changes in IL‐6 and/or IL‐11 expression, (12) but this proposal remains controversial (13–15) . It has also been proposed that these cytokines may also be involved in the pathogenesis of Paget's disease, (16) hyperparathyroidism, (17) rheumatoid arthritis, (18) and other bone diseases (19) .…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-11 Receptor Signaling Is Required for Normal Bone Remodeling

Sims

Jenkins

Nakamura

et al. 2005

Journal of Bone and Mineral Research

145

117

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IL-6 and -11 regulate bone turnover and have been implicated in estrogen deficiency-related bone loss. In this study, deletion of IL-11 signaling, but not that of IL-6, suppressed osteoclast differentiation, resulting in high trabecular bone volume and reduced bone formation. Furthermore, IL-11 signaling was not required for the effects of estradiol or estrogen deficiency on the mouse skeleton.Introduction: Interleukin (IL)-6 and -11 stimulate osteoclastogenesis and bone formation in vitro and have been implicated in bone loss in estrogen deficiency. Because of their common use of the gp130 co-receptor signaling subunit, the roles of these two cytokines are linked, and each may compensate for the absence of the other to maintain trabecular bone volume and bone cell differentiation. Materials and Methods:To determine the interactions in bone between IL-11 and IL-6 in vivo and whether IL-11 is required for normal bone turnover, we examined the bone phenotype of mature male and female IL-11 receptor knockout mice (IL-11R␣1

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Section: Resultsmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-11 Receptor Signaling Is Required for Normal Bone Remodeling

Sims

Jenkins

Nakamura

et al. 2005

Journal of Bone and Mineral Research

145

117

View full text Add to dashboard Cite

show abstract

“…This paracrine Met signaling activated IL-11 and upregulated the receptor activator of NF-κB ligand (RANKL) in osteoblast-like Saos2 cells. IL-11 inhibits bone formation (Hughes and Howells, 1993) and supports bone resorption (Shaughnessy et al, 2002). Further, heparin enhances IL-11 signaling through activation of ERK MAP kinase (Rajgopal et al, 2006), suggesting that syndecan-1 functions in an HS-dependent manner.…”

Section: Cancermentioning

confidence: 99%

Molecular functions of syndecan-1 in disease

2012

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Syndecan-1 is a cell surface heparan sulfate proteoglycan that binds to many mediators of disease pathogenesis. Through these molecular interactions, syndecan-1 can modulate leukocyte recruitment, cancer cell proliferation and invasion, angiogenesis, microbial attachment and entry, host defense mechanisms, and matrix remodeling. The significance of syndecan-1 interactions in disease is underscored by the striking pathological phenotypes seen in the syndecan-1 null mice when they are challenged with disease-instigating agents or conditions. This review discusses the key molecular functions of syndecan-1 in modulating the onset, progression, and resolution of inflammatory diseases, cancer, and infection.

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“…Since estrogens normally suppress the generation and activation of osteoclasts [4], bone remodelling is consecutively shifted towards resorption as seen in postmenopausal hormone deficiency. Further menopause-triggered effects are overexpression of pro-inflammatory cytokines (IL-6, IL-11, TNFa), reduced expression of the osteoclast suppressor TGF-b and the enlargement of the bone marrow pool of resorptive progenitor cells [5,6]. Despite the fact that these results add up to a conceivably pathogenetic concept in women that could be partially suitable for men, concise results from corresponding studies in males are still pending.…”

Section: Sex Hormonesmentioning

confidence: 99%

Of mice and men: pathophysiology of male osteoporosis

Patsch

Muschitz²,

Resch³

et al. 2007

The Journal of Men's Health & Gender

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In both old and young men osteoporosis is a severe but frequently neglected condition. This review deals with the multifactorial pathogenesis of impaired bone strength in men. Male bones are not only influenced by androgens, but, somewhat surprisingly -according to the current state of knowledge -female sex hormones may be the major players in calcified tissue remodelling. As a matter of principle, gender shapes bone geometry on a life-long basis. In men, age-dependant bone loss is outweighed by increased periosteal apposition. Contrary to women, the male gender-specific resorption pattern is mainly based on trabecular thinning. Therefore the connectivity remains rather intact, which again positively influences the biomechanical tissue properties and the resistance to fractures. Since affected patients often present with a family history of fractures or low bone density, the genetics of male osteoporosis is one of the main fields of interest in current bone research. Several gene polymorphisms involving the a1 chain of type 1 collagen (COLIA-1), aromatase, vitamin D receptor (VDR), low-density lipoprotein receptor-related protein 5 (LPR5) and the lactase phlorizin hydrolase (LCT) have recently been described. But apart from such exciting research novelties, the classical every-day violaters of both male and female bone health (vitamin D deficiency, low calcium intake and inadequate life-style) must still be taken into account.

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Neutralization of Interleukin-11 Activity Decreases Osteoclast Formation and Increases Cancellous Bone Volume in Ovariectomized Mice

Cited by 20 publications

References 40 publications

Interleukin-11 Receptor Signaling Is Required for Normal Bone Remodeling

Interleukin-11 Receptor Signaling Is Required for Normal Bone Remodeling

Molecular functions of syndecan-1 in disease

Of mice and men: pathophysiology of male osteoporosis

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