Estradiol and genistein antagonize the ovariectomy effects on skeletal muscle myosin heavy chain expression via ER-β mediated pathways

Velders, Martina; Solzbacher, M.; Schleipen, B.; Laudenbach, U.; Fritzemeier, Karl-Heinrich; Diel, Patrick

doi:10.1016/j.jsbmb.2010.03.059

Cited by 30 publications

(20 citation statements)

References 47 publications

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“…The effect of ERβ silencing was greater than that of ERα silencing. It seems that the effect of genistein on rat mandibular subchondral bone was preferentially mediated via ERβ activation, which is in keeping with the previous report that the effect of genistein on skeletal muscle myosin heavy chain expression was predominantly mediated through ERβ [46] .…”

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentsupporting

confidence: 90%

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Xing

Wang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats. Methods: Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10 -7 or 10 -4 mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using realtime PCR, and ER silencing was performed. Results: At both the low-and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment. Conclusion: In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.

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Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentsupporting

confidence: 90%

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Xing

Wang

et al. 2011

Acta Pharmacol Sin

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“…The present study showed that ERβ expression increased significantly following treatment with excess genistein, while ERα expression decreased at both the protein and mRNA levels. These results may indicate that genistein exerts its estrogenic activity in mandibular condylar cartilage mainly through ERβ, which is consistent with another recent finding that the effects of genistein on skeletal muscle major histocompatibility complex (MHC) expression was predominantly mediated through ERβ [30] . In summary, the present study demonstrated that excess genistein can suppress extracellular matrix synthesis and chondrocyte proliferation in rat mandibular condylar cartilage, resulting in thinner mandibular condylar cartilage.…”

Section: Discussionsupporting

confidence: 92%

Excess genistein suppresses the synthesis of extracellular matrix in female rat mandibular condylar cartilage

Xing

Dong

et al. 2012

Acta Pharmacol Sin

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Aim:To investigate the effect of excess genistein on the extracellular matrix in mandibular condylar cartilage of female rats in vivo. Methods: Female SD rats were administered through oral gavage with genistein (50 mg/kg) or placebo daily for 6 weeks. The morphological changes of temporomandibular joints were studied with HE staining. The expression of cartilage matrix compounds (aggrecan and collagen type II), estrogen-related molecules (aromatase, estradiol, ERα and ERβ) and proliferating cell nuclear antigen (PCNA) in mandibular condylar cartilage was detected using immunohistochemistry, ELISA and real-time PCR. Results: The genistein treatment significantly reduced the thickness of the posterior and middle regions of mandibular condylar cartilage, and decreased the expression of collagen type II, aggrecan and PCNA. Compared with the control group, the estradiol content and expression levels of the key estradiol-synthesizing enzyme aromatase in the genistein-treatment group were significantly decreased. The genistein treatment significantly increased the expression of ERβ, but decreased the expression of ERα. Conclusion: Excess genistein suppresses extracellular matrix synthesis and chondrocytes proliferation, resulting in thinner mandibular condylar cartilage. These effects may be detrimental to the ability of mandibular condylar cartilage to adapt to mechanical loads.

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“…How the effects of E 2 may differ among fibers with various isoforms of the myosin heavy and light chains is not presently clear, nor is the impact of estrogen status on expression of the various myosin isoforms. There are reports of OVX-related shifts toward slower isoforms/fiber types (11,22,42), toward faster isoforms/fiber types (29,45,61), and no changes in myosin isoforms/fiber types (9,39,42,47,66). Importantly, when such shifts are detected they are modest, in the magnitude of 10% or less, and thus likely have little impact on the extent of force potentiation reported here.…”

Section: Discussionmentioning

confidence: 53%

Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice

Lai

Collins

Colson

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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-Impairment of skeletal muscle function has been associated with changes in ovarian hormones, especially estradiol. To elucidate mechanisms of estradiol on skeletal muscle strength, the hormone's effects on phosphorylation of the myosin regulatory light chain (pRLC) and muscle contractility were investigated, hypothesizing an estradiol-specific beneficial impact. In a skeletal muscle cell line, C 2C12, pRLC was increased by 17␤-estradiol (E 2) in a concentration-dependent manner. In skeletal muscles of C57BL/6 mice that were E 2 deficient via ovariectomy (OVX), pRLC was lower than that from ovary-intact, sham-operated mice (Sham). The reduced pRLC in OVX muscle was reversed by in vivo E 2 treatment. Posttetanic potentiation (PTP) of muscle from OVX mice was low compared with that from Sham mice, and this decrement was reversed by acute E 2 treatment, demonstrating physiological consequence. Western blot of those muscles revealed that low PTP corresponded with low pRLC and higher PTP with greater pRLC. We aimed to elucidate signaling pathways affecting E 2-mediated pRLC using a kinase inhibitor library and C 2C12 cells as well as a specific myosin light chain kinase inhibitor in muscles. PI3K/Akt, MAPK, and CamKII were identified as candidate kinases sensitive to E 2 in terms of phosphorylating RLC. Applying siRNA strategy in C 2C12 cells, pRLC triggered by E 2 was found to be mediated by estrogen receptor-␤ and the G protein-coupled estrogen receptor. Together, these results provide evidence that E 2 modulates myosin pRLC in skeletal muscle and is one mechanism by which this hormone can affect muscle contractility in females. estrogen; estrogen receptor; kinase; post tetanic potentiation; RLC OVARIAN HORMONE DEFICIENCY is related to muscle dysfunction and loss of strength. For example, declines in strength are accelerated around the time of menopause (35,41,51), and skeletal muscles of postmenopausal women on estrogen-based hormone therapy are stronger than those not on hormone therapy (10,17,49). In mouse models, contractile characteristics are impaired in muscles of ovariectomized compared with sham-operated mice (16,38,39,53,65). It was suggested (41) and subsequently demonstrated that ovarian hormones influence muscle strength by directly affecting the function of contractile proteins (43,66), particularly the structure and function of myosin (38,39). Among the ovarian hormones, 17␤-estradiol (E 2 ) appears to be the key hormone, because it reverses muscle weakness and contractile protein dysfunction caused by ovariectomy. Specifically, reduced muscle and contractile protein functions were restored when E 2 was administered to ovariectomized mice (16,38,53). In a chemical model of premature aging, of which the ovaries of young adult mice were locally and specifically induced to be senescent, E 2 treatment improved some muscle contractile functions (18). Although these studies have demonstrated that E 2 impacts muscle and myosin functions, the molecular mechanisms by which this hormone affects the structure a...

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Estradiol and genistein antagonize the ovariectomy effects on skeletal muscle myosin heavy chain expression via ER-β mediated pathways

Cited by 30 publications

References 47 publications

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Excess genistein suppresses the synthesis of extracellular matrix in female rat mandibular condylar cartilage

Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice

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