Mammalian Mature Osteoclasts as Estrogen Target Cells

Miyata, Hiroshi; Yuasa, Tatsuhisa; Kameda, Takashi; Miyazawa, Koshi; Nakamaru, Yukiya; Shiokawa, Miho; Mori, Yoshihito; Yamada, Takeo; Miyata, Katsunobu; Shindo, Hiroyuki; Azuma, Hirohiko; Hakeda, Yoshiyuki; Kumegawa, Masayoshi

doi:10.1006/bbrc.1996.0947

Cited by 89 publications

(51 citation statements)

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“…These estrogen effects on osteoclasts were blocked by treatment with antiestrogens. Moreover, Northern blot analysis demonstrated abundant estrogen receptor ␣ (ER ␣ ) 1 mRNA expression in isolated osteoclasts, suggesting that estrogen may also have a direct impact on osteoclasts (22)(23)(24). The data presented here indicate that estrogen inhibits osteoclastic bone resorption activity in part by targeting osteoclasts directly to undergo apoptosis through ER-mediated mechanisms.…”

Section: Discussionmentioning

confidence: 73%

Bacterial Chitinolytic Communities Respond to Chitin and pH Alteration in Soil

Kielak

Cretoiu

Semenov

et al. 2013

Appl Environ Microbiol

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SummaryEstrogen deficiency causes bone loss, which can be prevented by estrogen replacement therapy. Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 ␤ -estradiol (E 2 ) was able to directly inhibit osteoclastic bone resorption. At concentrations effective for inhibiting bone resorption, E 2 also directly induced osteoclast apoptosis in a dose-and time-dependent manner. ICI164,384 and tamoxifen, as pure and partial antagonists, respectively, completely or partially blocked the effect of E 2 on both inhibition of osteoclastic bone resorption and induction of osteoclast apoptosis. These data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direct induction of apoptosis of the bone-resorbing osteoclasts by an estrogen receptormediated mechanism.

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Section: Discussionmentioning

confidence: 73%

Bacterial Chitinolytic Communities Respond to Chitin and pH Alteration in Soil

Kielak

Cretoiu

Semenov

et al. 2013

Appl Environ Microbiol

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“…(30) Continuous erosion over bone slices without leaving behind collagen remnants is reminiscent of continuous erosion over bone trabeculae and absence of collagen leftovers in vivo, where maybe factors from surrounding cells play the role of GCs in our experiments. (38)(39)(40) One may speculate that the mechanism for stopping the continuation of erosion in physiology is via factors that reduce collagenolysis such as estrogen, which was reported to lower cathepsin K levels (41) and to lead to more collagen in the pits. (42) Thus the extent of erosion over bone surfaces may be regulated by the balance of factors either upregulating or downregulating cathepsin K. Therefore, in patients treated with high-dose GC, a cathepsin K inducer, (7) continuous erosion may be strongly accentuated, whereas in postmenopausal patients, cathepsin K inhibitors decrease bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle

Søe

Delaissé

2010

Journal of Bone and Mineral Research

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Osteoclasts are known to exert their resorptive activity through a so-called resorption cycle consisting of alternating resorption and migration episodes and resulting typically in the formation of increasing numbers of discrete round excavations on bone slices. This study shows that glucocorticoids deeply modify this resorptive behavior. First, glucocorticoids gradually induce excavations with a trenchlike morphology while reducing the time-dependent increase in excavation numbers. This indicates that glucocorticoids make osteoclasts elongate the excavations they initiated rather than migrating to a new resorption site, as in control conditions. Second, the round excavations in control conditions contain undegraded demineralized collagen as repeatedly reported earlier, whereas the excavations with a trenchlike morphology generated under glucocorticoid exposure appear devoid of leftovers of demineralized collagen. This indicates that collagenolysis proceeds generally at a lower rate than demineralization under control conditions, whereas collagenolysis rates are increased up to the level of demineralization rates in the presence of glucocorticoids. Taking these observations together leads to a model where glucocorticoid-induced increased collagenolysis allows continued contact of osteoclasts with mineral, thereby maintaining resorption uninterrupted by migration episodes and generating resorption trenches. In contrast, accumulation of demineralized collagen, as prevails in controls, acts as a negative-feedback loop, switching resorptive activity off and promoting migration to a new resorption site, thereby generating an additional resorption pit. We conclude that glucocorticoids change the osteoclastic resorption mode from intermittent to continuous and speculate that this change may contribute to the early bone fragilization of glucocorticoid-treated patients. ß

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“…The antiosteoporotic actions of estrogen are complex but ultimately result in a suppression of osteoclast-mediated (OC-mediated) bone resorption (4). Estrogen acts on other bone cell types to indirectly influence OC resorption; however, evidence for a direct action of estrogen on OCs has also been suggested by studies documenting that isolated avian and mammalian OCs and OC-like cells possess estrogen receptors and are estrogen responsive (5)(6)(7)(8)(9). In particular, estrogen has decreased key OC-resorptive enzymes, inhibited OC bone resorption (6)(7)(8)10), and promoted OC apoptosis (11), processes that favor a positive bone balance.…”

Section: Introductionmentioning

confidence: 99%

“…Because the affinity of 17β-estradiol for its receptor is in the nanomolar range, estrogen has been commonly administered in vitro at ≥10 -8 M to achieve receptor saturation, leading to rapid and maximal effects (7). Although physiological estrogen concentrations have modulated lysosomal enzyme levels, TGF-β production, and bone resorption in isolated OCs from mice (65), rabbits (8), and chick hatchlings (10,66,67), higher estrogen levels have been required to modulate hOC or hOCL cells (68,69). Possibly, high estrogen concentrations may be needed to influence hOCL cells in vitro, as hOCL cells, in marked contrast to hOBs, can create a proestrogenic local microenvironment, reaching as high as 10-fold serum midcyclic estradiol peaks, independent from actual circulating levels of estrogen (70).…”

Section: Figurementioning

confidence: 99%

Estrogen’s bone-protective effects may involve differential IL-1 receptor regulation in human osteoclast-like cells

Sunyer¹,

Lewis²,

Collin‐Osdoby³

et al. 1999

J. Clin. Invest.

124

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Declining estrogen levels during the first postmenopausal decade lead to rapid bone loss and increased fracture risk that can be reversed by estrogen replacement therapy. The bone-protective effects of estrogen may involve suppression of inflammatory cytokines that promote osteoclastogenesis and bone resorption, such as IL-1, TNF-α, and IL-6. We investigated whether estrogen modulates IL-1 actions on human osteoclasts (OCs) and other bone cell types. Isolated human OCs and primary bone marrow-derived OC-like cells expressed both the signaling (IL-1RI) and decoy (IL-1RII) IL-1 receptors, whereas only IL-1RI was detected in osteoblasts. IL-1RII/IL-1RI mRNA ratios and release of soluble IL-1RII (sIL-1RII) were lower in OC-like cells derived from women in the late postmenopausal period compared with younger women, but were unrelated to male donor age, suggesting that estrogen might play a role in regulating IL-1 receptor levels in vivo. Estrogen directly reduced in vitro OC-like cell IL-1RI mRNA levels while increasing IL-1RII mRNA levels and sIL-1RII release. These estrogenic events were associated with inhibited IL-1-mediated cytokine (IL-8) mRNA induction and cell survival, i.e., increased apoptosis. In contrast, estrogen did not alter IL-1R levels or IL-1 responsiveness in primary human osteoblasts or bone marrow stromal cells. We conclude that one novel mechanism by which estrogen exerts bone-protective effects may include a selective modulation of IL-1R isoform levels in OC or OC-like cells, thereby reducing their IL-1 responsiveness and cell survival. Conversely, this restraint on IL-1 actions may be lost as estrogen levels decline in aging women, contributing to an enhanced OC-mediated postmenopausal bone loss. IL-1 is a potent in vivo and in vitro stimulator of bone resorption owing to its promotion of OC differentiation, OC-resorptive activity (34,35), and OC cell survival (36,37). It has been postulated that IL-1 acts indirectly on OCs through the release of soluble factor(s) from osteoblasts and other marrow cells (38). For example, high-affinity binding of IL-1 to IL-1 signaling receptors expressed on osteoblasts leads to a paracrine modulation of OC development and activity (34). However, some evidence also exists for a direct effect of IL-1 on OCs. IL-1 has been shown to raise intracellular Ca 2+ levels in isolated individual rabbit OCs (39) and to activate NF-κB-like transcription factors in purified murine OC-like cells (40); IL-1 receptor mRNA has been detected in rodent OCs by in situ hybridization (41); and IL-1 treatment of purified human OC-like cells has stimulated the release of 43). The biologic effects of IL-1 on bone depend on complex interactions among many factors, including IL-1α, IL-1β, IL-1Ra, IL-1 receptors, and IL-1 receptor accessory protein. Two distinct IL-1 receptors are known: the type I, or signaling, receptor (IL-1RI) that mediates cellular responses to IL-1 and binds equally well IL-1 agonist and antagonist; and the type II, or decoy, receptor (IL-1RII) that preferentially b...

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Mammalian Mature Osteoclasts as Estrogen Target Cells

Cited by 89 publications

References 0 publications

Bacterial Chitinolytic Communities Respond to Chitin and pH Alteration in Soil

Bacterial Chitinolytic Communities Respond to Chitin and pH Alteration in Soil

Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle

Estrogen’s bone-protective effects may involve differential IL-1 receptor regulation in human osteoclast-like cells

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