Interleukin-11 receptor signaling is required for normal bone remodeling
Details
Publication Year 2005-07, Volume 20, Issue #7, Page 1093-1102
Journal Title
JOURNAL OF BONE AND MINERAL RESEARCH
Publication Type
Journal Article
Abstract
IL-6 and -11 regulate bone turnover and have been implicated in estrogen deficiency-related bone loss. In this study, deletion of IL-11 signalling, but not that 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 alpha 1(-/-)) and compared with the bone phenotype of IL-6(-/-) mice and mice lacking both IL-6 and IL-11R alpha. To determine whether IL-11 is required for the effects of estrogen on trabecular bone, mature IL-11R alpha 1(-/-) mice were ovariectomized and treated with estradiol. Results: In both male and female IL-11R alpha 1(-/-) mice, trabecular bone volume was significantly higher than that of wildtype controls. This was associated with low bone resorption and low bone formation, and the low osteoclast number generated by IL-11R alpha 1(-/-) precursors was reproduced in ex vivo cultures, whereas elevated osteoblast generation was not. Neither trabecular bone volume nor bone turnover was altered in IL-6(-/-) mice, and compound IL-6(-/-):IL-11R alpha 1(-/-) mice showed an identical bone phenotype to IL-11R alpha 1(-/-) mice. The responses of IL-11R alpha 1(-/-) mice to ovariectomy and estradiol treatment were the same as those observed in wildtype mice. Conclusions: IL-11 signaling is clearly required for normal bone turnover and normal trabecular bone mass, yet not for the effects of estradiol or estrogen deficiency on the skeleton. In the absence of IL-11R alpha, increased trabecular bone mass seems to result from a cell lineage-autonomous reduction in osteoclast differentiation, suggesting a direct effect of IL-11 on osteoclast precursors. The effects of IL-11R alpha deletion on the skeleton are not mediated or compensated for by changes in IL-6 signaling.
Publisher
AMER SOC BONE & MINERAL RES
Keywords
OSTEOCLAST FORMATION; OSTEOBLASTIC CELLS; INHIBITS ADIPOGENESIS; MARROW CULTURES; DEFICIENT MICE; STROMAL CELLS; IN-VITRO; IL-6; GP130; DIFFERENTIATION
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Creation Date: 2005-07-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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